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Ian C M Maclennan - One of the best experts on this subject based on the ideXlab platform.
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Brief Definitive Report Low-level Hypermutation in T Cell–independent Germinal Centers Compared with High Mutation Rates Associated with T Cell–dependent Germinal Centers
2013Co-Authors: Kai-michael Toellner, Dale R Taylor, William E. Jenkinson, Mahmood Khan, Daniel -y. M. Sze, David M. Sansom, Carola G. Vinuesa, Ian C M MaclennanAbstract:Exceptionally germinal center formation can be induced without T cell help by polysaccharidebased antigens, but these germinal centers involute by massive B cell apoptosis at the time Centrocyte selection starts. This study investigates whether B cells in germinal centers induced by the T cell–independent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation in their immunoglobulin V region genes. Positive controls are provided by comparing germinal centers at the same stage of development in carrier-primed mice immunized with a T cell–dependent antigen: NP protein conjugate. False positive results from background germinal centers and false negatives from non-B cells in germinal centers were avoided by transferring B cells with a transgenic B cell receptor into congenic controls not carrying the transgene. By 4 d after immunization, hypermutation was well advanced in the T cell–dependent germinal centers. By contrast, the mutation rate for T cell–independent germinal centers was low, but significantly higher than in NP-specific B cells from nonimmunized transgenic mice. Interestingly, a similar rate of mutation was seen in extrafollicular plasma cells at this stage. It is concluded that efficient activation of hypermutation depends on interaction with T cells, but some hypermutation may be induced without such signals, even outside germinal centers. Key words: spleen • plasma cells • DNA mutational analysis • adoptive cell transfer • immunizatio
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Centrocytes rapidly adopt a memory b cell phenotype on co culture with autologous germinal centre t cell enriched preparations
International Immunology, 1996Co-Authors: Montserrat Casamayorpalleja, Jean Feuillard, Jennifer Ball, Marion Drew, Ian C M MaclennanAbstract:B cells, after mutating their Ig V-region genes in germinal centres (GC), undergo apoptosis, unless they receive antigen-dependent selection signals. The signals appear to be delivered by GC T cells, require CD40 ligand expression and may induce differentiation to memory cells. Cultured GC B cells are prevented from entering apoptosis by ligating their surface CD40, but the resulting phenotype is not that associated with B cells found in vivo. Conversely, GC B cells rapidly adopt a memory B cell phenotype on culture with autologous memory CD4+ T cells that have been induced to express CD40 ligand transiently. This effect is prevented by blocking CD40 ligand. Naive CD4+ T cells, induced to express CD40 ligand, do not prevent GC B cells undergoing apoptosis.
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isolation and characteristics of tonsil centroblasts with reference to ig class switching
International Immunology, 1995Co-Authors: Jean Feuillard, Montserrat Casamayorpalleja, Dale R Taylor, Gerald D Johnson, Ian C M MaclennanAbstract:Most tonsil B cells have high levels of surface CD44 but this molecule is either expressed at low levels or is absent from germinal centre B cells (GCB). On average 62% of isolated GCB were found to be CD44- and the remainder CD44low. Most CD44- GCB were in cell cycle, indicating that they were centroblasts, while Centrocytes, non-dividing GCB, were mainly CD44low. Immunohistological analysis confirms that Centrocytes, which are located in the light zone of germinal centres, express low levels of CD44, while centroblasts, cells of the dark zone, are CD44-. While most CD77high GCB are centroblasts and CD77low GCB Centrocytes, many centroblasts and Centrocytes express intermediate levels of CD77, making this less reliable than CD44 for discriminating between these cells. Most CD44low and CD44- GCB were shown to have undergone Ig switch recombination in vivo. This indicates that switch recombination is independent of the maturation of centroblasts to Centrocytes and precedes the signals that induce GCB to differentiate to plasma cells or memory B cells. The average rate of entry of the CD44- GCB fraction to apoptosis on culture at 37 degrees C was faster than that of the total GCB preparation. It is suggested that this may reflect strict stromal-dependence of centroblasts while Centrocytes have to survive for long enough to have the chance of receiving antigen-specific selection signals. Inhibition of apoptosis by CD40 mAb with IL-4 or phorbol myristate acetate with ionomycin was similar in the CD44- and CD44low preparations.
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sites of specific b cell activation in primary and secondary responses to t cell dependent and t cell independent antigens
European Journal of Immunology, 1991Co-Authors: Yongjun Liu, Jun Zhang, Peter J L Lane, Eric Y T Chan, Ian C M MaclennanAbstract:Techniques which identify hapten-specific B cells in tissues have been used to determine the sites of B cell activation in rat spleens in response to T cell-dependent (TD) antigens and T cell-independent type-1 (TI-1) antigens. Surface-associated hapten binding by specific memory B cells and. B blasts was distinguished from the strong cytoplasmic hapten binding by specific plasma cells and plasmablasts. Blast cells in S phase were identified in tissue sections by staining cells which had been pulse labeled in vivo with 5-bromo-2′-deoxyuridine. Hapten-specific B blast cells are found in three sites: (a) around interdigitating cells in the T cell-rich zones; (b) in the follicular dendritic cell network and (c) in association with macrophages in the red pulp. Hapten-binding memory B cells, which are not in cell cycle, accumulate in the marginal zones and to a lesser extent the follicular mantles in response to TD and TI-1 antigens. The hapten-specific blast response in T zones is confined to the first few days after antigen is given and is low for primary responses to TD antigens, but massive on secondary challenge, when marginal zone memory B cells migrate to the T zones. Both the primary and secondary T zone responses to TI-1 antigens are impressive and in these responses hapten-specific B blasts are also found in the splenic red pulp. The follicular response to TD antigens starts with a small number of B blasts (fewer than five) entering each follicle. These increase in number exponentially so that by the 4th day after immunization they fill the follicle. The oligoclonality of the response is shown in simultaneous responses to two haptens where 6%–31% of the follicles on day 3 after immunization contain blasts specific for only one of the two haptens. During the 4th day classical zonal pattern of germinal centers develops. The surface immunoglobulin-positive B blasts are lost from the follicle center, while one pole of the follicular dendritic cell network fills with surface immunoglobulin-negative centroblasts. Centroblasts do not increase in numbers but divide to give rise to Centrocytes, which re-express slg and migrate into the follicular dendritic cell network. Cell kinetic studies indicate that the Centrocyte population is renewed from centroblasts every 7 h. Centrocytes either leave the germinal center within this time or die in situ. It is probable that the centroblasts and Centrocytes are derived from the small number of B blasts which initiate the follicular reaction, for the Centrocytes show the same oligoclonality observed at the B blast stage. The germinal center reaction declines gradually and 3 weeks after immunization centroblasts and Centrocytes are no longer seen. At this time small clusters of B blasts can be found proliferating in the follicular dendritic cell network. These secondary B blasts characterize the third phase of the follicular reaction, which continues throughout the established phase of TD responses. Some follicular response is seen to TI-1 antigens but this is much less dramatic than that seen during TD responses.
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recombinant 25 kda cd23 and interleukin 1α promote the survival of germinal center b cells evidence for bifurcation in the development of Centrocytes rescued from apoptosis
European Journal of Immunology, 1991Co-Authors: Yongjun Liu, Jennifer A Cairns, Michelle J Holder, Sandra D Abbot, Katherin U Jansen, Jeanyves Bonnefoy, John R Gordon, Ian C M MaclennanAbstract:Germinal centers contain a proliferating pool of centroblasts which give rise to non-dividing Centrocytes. Centrocytes are programmed to die by apoptosis unless they receive a positive signal for rescue. Rescue, in vivo, is likely to be dependent, initially, on interaction with antigen held on follicular dendritic cells (FDC). A subset of FDC located in that part of the germinal center furthest from centroblasts is particularly rich in CD23. Supernatants containing high levels of soluble CD23 were found not only to encourage the survival of germinal center B cells but also to promote their differentiation toward a plasmacytoid morphology; these activities were diminished following removal of CD23 from the supernatants. Recombinant 25-kDa CD23 was initially found to be incapable of providing the signal for germinal center cell development but on the addition of interleukin 1α which, by itself, was inactive, rescue and differentiation of germinal center B cells were now achieved. Apoptosis in germinal center cells could also be prevented by the ligation of surface CD40 with monoclonal antibody: however, rescue via this pathway was not accompanied by plasmacytoid differentiation. These findings provide a functional rationale to the high level expression of CD23 found within a discrete subset of FDC and indicate a bifurcation in the development of germinal center B cells following their rescue from apoptosis.
Nobuhide Masawa - One of the best experts on this subject based on the ideXlab platform.
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Incidental MALT Type Lymphoma Exhibiting Prominent Plasma Cell Differentiation Associated with Hashimoto’s Thyroiditis.
2013Co-Authors: A Two, Nobuhide Masawa, M. Kojima, K. Shimizu, N. MasawaAbstract:Ó The Author(s) 2008. This article is published with open access at Springerlink.com Abstract We present here two cases of incidental extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT lymphoma) showing prominent plasma cell differentiation associated with Hashimoto’s thyroiditis (HT). Histological examination demonstrated that both lesions exhibited HT including lymphoplasmacytic infiltration with the formation of germinal centers, destruction of the normal thyroid follicular architecture, Hürthle cell changes, and squamous metaplasia. The dominant tumor nodules of both cases contained large, well-circumscribed but unencapsulated aggregation of mature plasma cells and scattered Centrocyte-like cells (CCL-cells). Both lesions contained a few lymphoepithelial lesions. Moreover, immunohistochemical study demonstrated that plasma cells and CCL-cells of these two lesions contained monotypic intracytoplasmi
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marginal zone b cell lymphoma of minor salivary gland representing tumor forming amyloidosis of the oral cavity a case report
Journal of Oral Pathology & Medicine, 2006Co-Authors: Masaru Kojima, Shiro Sugihara, Misa Iijima, Takayuki Ono, Takashi Yoshizumi, Nobuhide MasawaAbstract:We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma arising from the minor salivary gland of the oral cavity exhibiting tumor-forming amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4-year history of a left soft palate mass. Despite multiple and multifocal recurrences including the lip, soft palate, tongue, oral base and vocal code and soft palate, the tumor remained localized in the upper aerodigestive tract, and the patient did not develop multiple myeloma during the course of disease. Histologically, the majority of the lesion was occupied by amyloid deposition. Only the periphery of the lesion contained numerous plasmacytoid cells, along with occasional Centrocyte-like cells. In addition, lymphoepithelial lesion and follicular colonization were noted. The present case indicates that primary minor salivary gland MALT-type lymphoma appears to be the cause of tumor-forming amyloidosis of the upper aerodigestive tract including the larynx.
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nodal marginal zone b cell lymphoma resembling plasmacytoma arising from a plasma cell variant of localized castleman s disease a case report
Apmis, 2002Co-Authors: Masaru Kojima, Shigeo Nakamura, Shiro Sugihara, Kazuhiko Shimizu, Noriyuki Sakata, Yoshio Suda, Yoshio Kasuga, Nobuhide MasawaAbstract:: Nodal marginal zone B-cell lymphoma (NMZBL) occasionally represents prominent plasma cell differentiation. Recently, primary lymph node plasmacytoma has been suggested to represent an extremely plasmacytic differentiation of NMZBL. We here report a case of NMZBL showing histological features resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease (PCLCD). The patient was a 69-year-old Japanese female with a 20-year history of a right inguinal mass. Histologically, a prominent proliferation of plasma cells occupied the interfollicular area of the central portion of the lymph node, whereas Centrocyte-like (CCL) cells were the main cellular component in the peripheral portion of the lymph node. Although most of the plasma cells were mature 'Marshalko-type', occasional atypical forms with enlarged nuclei were also present. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry study revealed that both plasma cells and some CCL cells had a monotypic intracytoplasmic lambda light chain. When monoclonal plasma cell infiltration is observed in PCLCD, the light chains are mostly restricted to the lambda chain. This case suggests that some plasma cell-containing tumors arising from PCLCD may represent a variant of NMZBL.
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marginal zone b cell lymphomas of waldeyer s ring a report of two tonsillectomy cases resembling histomorphological features of inflammatory lesions
Pathology Research and Practice, 2001Co-Authors: Masaru Kojima, Shigeo Nakamura, Kazuhiko Shuimizu, Hideaki Itoh, Nobuhide MasawaAbstract:We identified two cases of lymphoma of the mucosa-associated lymphoid tissue (MALT) type in 11 tonsillectomy specimens of primary B cell lymphoma of Waldeyer's ring. Both patients were Japanese females presenting with bilateral enlargement of the palatine tonsils. One had a history of chronic otitis media. In that case, the lesion was characterized by an extrafollicular growth pattern with marginal zone-like arrangement. The tumor was mainly composed of medium-sized cells with round or indented nuclei with scant cytoplasm (Centrocyte-like cells). In the other patient, most tumor cells were mature plasma cells, plasmacytoid cells, proplasmacytes, and immunoblasts with scattered Centrocyte-like cells. Tropism of tumor cells for the epithelium was noted in both lesions. Primary marginal zone B cell lymphoma of the MALT type arising from Waldeyer's ring has rarely been reported in the literature, causing certain diagnostic problems. Various florid reactive lymphoproliferative disorders, including chronic tonsillitis and infectious mononucleosis, should be differentiated from this type of primary Waldeyer's ring lymphoma.
Masaru Kojima - One of the best experts on this subject based on the ideXlab platform.
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cytologic findings of primary thyroid malt lymphoma with extreme plasma cell differentiation fna cytology of two cases
Diagnostic Cytopathology, 2009Co-Authors: C Sadayuki M I A C Kaba, Masaru Kojima, Mitsuyoshi Hirokawa, M Seiji D Kuma, C Miyoko T Maekawa, C Yukari T Yanase, Akira MiyauchiAbstract:We report fine-needle aspiration cytology (FNAC) obtained from two cases of mucosa-associated lymphoid tissue (MALT) lymphoma with extreme plasma cell differentiation. The patients were 61-year-old and 69-year-old Japanese women presenting with thyroid swelling. The smears contained numerous plasma cells, lymphocytes with plasma cell differentiation and scattered Centrocyte-like (CCL) cells. In addition, one case demonstrated occasional atypical giant plasma cells. Occasional intranuclear inclusions (Dutcher bodies) of the plasma cells were observed in the other case. A few cytologic lymphoepithelial lesions-clusters (originating from lymphoepithelial lesions in histology) were also observed in one case. Plasma cells occupied approximately 10% in all of the lymphoid populations in FNAC specimens of Hashimoto thyroiditis, whereas, both cases demonstrated approximately 45% plasma cells and lymphocytes with plasma cell differentiation of all lymphocytes.The cytomorphologic findings of both cases were similar to those of plasmacytoma of the thyroid. However, immunohistochemical and flow cytometry studies demonstrated that both cases were MALT lymphoma with extreme plasma cell differentiation. From a therapeutic perspective, it is important to discriminate MALT lymphoma from plasmacytoma.
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marginal zone b cell lymphoma of minor salivary gland representing tumor forming amyloidosis of the oral cavity a case report
Journal of Oral Pathology & Medicine, 2006Co-Authors: Masaru Kojima, Shiro Sugihara, Misa Iijima, Takayuki Ono, Takashi Yoshizumi, Nobuhide MasawaAbstract:We report here a case of mucosa-associated lymphoid tissue (MALT)-type lymphoma arising from the minor salivary gland of the oral cavity exhibiting tumor-forming amyloidosis. The patient was a 64-year-old Japanese woman who presented with 4-year history of a left soft palate mass. Despite multiple and multifocal recurrences including the lip, soft palate, tongue, oral base and vocal code and soft palate, the tumor remained localized in the upper aerodigestive tract, and the patient did not develop multiple myeloma during the course of disease. Histologically, the majority of the lesion was occupied by amyloid deposition. Only the periphery of the lesion contained numerous plasmacytoid cells, along with occasional Centrocyte-like cells. In addition, lymphoepithelial lesion and follicular colonization were noted. The present case indicates that primary minor salivary gland MALT-type lymphoma appears to be the cause of tumor-forming amyloidosis of the upper aerodigestive tract including the larynx.
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mucosa associated lymphoid tissue lymphoma of the esophagus case report and review of the literature
Hepato-gastroenterology, 2004Co-Authors: Tatsuya Miyazaki, Masaru Kojima, Hiroyuki Kato, Norihiro Masuda, Masanobu Nakajima, Ryokuhei Manda, Minoru Fukuchi, Katsuhiko Tsukada, Takashi Nakajima, Hiroyuki KuwanoAbstract:: We report the histomorphologic and immunohistochemical features of another case of mucosa-associated lymphoid tissue (MALT) lymphoma arising from the esophagus and discuss the problems of differential diagnosis. The patient was a 49-year-old man, who had no gastrointestinal symptoms. On endoscopy, a smooth-surfaced, semibulbous lesion was found 36 cm from the incisors. We performed radical resection of this submucosal tumor with video-assisted thoracoscopic surgery for the purpose of diagnosis and treatment. The immunophenotype of the Centrocyte-like-cells was CD20+, BCL2+, CD5-, CD10-, CD23- CD45RO- and cyclin D1-. Diffuse immunostaining of bcl-2 was detected in the nuclei of the tumor cells without lymph follicles. Southern blotting analyses of the IgH gene detected a single dominant band indicative of a clonal IgH rearrangement. From the pathological, immunohistochemical, and molecular biological features we concluded that the tumor was a MALT lymphoma. Only three cases of primary esophageal MALT lymphoma have been reported to date. On the basis of the present case and the three previously reported cases, we suggest that MALT lymphoma of the esophagus is usually an elevated type. The spectrum of sites in which gastrointestinal MALT lymphoma occurs should be expanded to include the esophagus.
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primary marginal zone b cell lymphoma of the lymph node resembling plasmacytoma arising from a plasma cell variant of castleman s disease a clinicopathological and immunohistochemical study of seven patients
Apmis, 2002Co-Authors: Masaru Kojima, Shigeo Nakamura, Shiro Sugihara, Tadashi Motoori, Shunichi Shimano, Kayako Murayama, Yoshio Tamaki, Kazuhiko Shimizu, Tetsunari Oyama, Noriyuki SakataAbstract:: Nodal marginal zone B-cell lymphomas (NMZBL) occasionally represent prominent plasma cell differentiation. Recently, we presented a patient with NMZBL who exhibited histological features that resembled plasmacytoma arising from a localized plasma cell variant of Castleman's disease. To further clarify the clinicopathological, immunohistochemical, and genotypical findings, we studied seven such patients. Clinically, these patients were characterized by localized disease and an indolent clinical course with a slowly growing bulky mass in the affected lymph node. Only one patient exhibited paraproteinemia. Histologically, the lesions were characterized by numerous evenly distributed germinal centers in extensive sheets of plasma cells. Various numbers of Centrocyte-like (CCL) cells arranged in a marginal zone distribution pattern occupied the peripheral region of the lymph node. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry showed that all of the lesions contained a monoclonal plasma cell population. In three tumors, a number of the CCL cells had a similar light chain restriction pattern to that observed in plasma cells. Two of the four patients evaluated exhibited clonal bands for the IgH gene by polymerase chain reaction assay. Moreover, the presence of surface IgM+, IgD- and CD27+ CCL- cells suggests that these tumors are derived from memory B-lymphocytes.
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nodal marginal zone b cell lymphoma resembling plasmacytoma arising from a plasma cell variant of localized castleman s disease a case report
Apmis, 2002Co-Authors: Masaru Kojima, Shigeo Nakamura, Shiro Sugihara, Kazuhiko Shimizu, Noriyuki Sakata, Yoshio Suda, Yoshio Kasuga, Nobuhide MasawaAbstract:: Nodal marginal zone B-cell lymphoma (NMZBL) occasionally represents prominent plasma cell differentiation. Recently, primary lymph node plasmacytoma has been suggested to represent an extremely plasmacytic differentiation of NMZBL. We here report a case of NMZBL showing histological features resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease (PCLCD). The patient was a 69-year-old Japanese female with a 20-year history of a right inguinal mass. Histologically, a prominent proliferation of plasma cells occupied the interfollicular area of the central portion of the lymph node, whereas Centrocyte-like (CCL) cells were the main cellular component in the peripheral portion of the lymph node. Although most of the plasma cells were mature 'Marshalko-type', occasional atypical forms with enlarged nuclei were also present. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry study revealed that both plasma cells and some CCL cells had a monotypic intracytoplasmic lambda light chain. When monoclonal plasma cell infiltration is observed in PCLCD, the light chains are mostly restricted to the lambda chain. This case suggests that some plasma cell-containing tumors arising from PCLCD may represent a variant of NMZBL.
Irina L. Grigorova - One of the best experts on this subject based on the ideXlab platform.
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CCL3 Promotes Germinal Center B Cells Sampling by Follicular Regulatory T Cells in Murine Lymph Nodes.
Frontiers in immunology, 2018Co-Authors: Zachary L. Benet, Matangi Marthi, Jackson S. Turner, Jahan B. Gabayre, Michael I. Ivanitskiy, Sahil S. Sethi, Irina L. GrigorovaAbstract:Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) Centrocytes. However, the role of CCL3/4 for Centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. Two-photon imaging revealed that B cells-intrinsic production of CCL3 promotes their probing by follicular regulatory T cells (Tfr) within GCs of murine lymph nodes. Overall this study suggests that CCL3 facilitates direct interactions of foreign antigen-specific GC B cells and their negative regulation with Tfr cells in vivo.
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CCL3 promotes germinal center B cells sampling by follicular regulatory T cells.
2018Co-Authors: Zachary L. Benet, Matangi Marthi, Jackson S. Turner, Jahan B. Gabayre, Michael I. Ivanitskiy, Sahil S. Sethi, Irina L. GrigorovaAbstract:Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) Centrocytes. However, the role of CCL3/4 for Centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. In vivo CCL3 is not required for Tfr cells recruitment of into the GC light zone. However, B cells- intrinsic production of CCL3 promotes their direct interactions and negative regulation by follicular regulatory T cells (Tfr) within GCs.
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ccl3 promotes germinal center b cells sampling by follicular regulatory t cells and ensures optimal humoral response
bioRxiv, 2018Co-Authors: Irina L. Grigorova, Zachary L. Benet, Matangi Marthi, Jackson S. Turner, Jahan B. Gabayre, Michael I. Ivanitskiy, Sahil S. SethiAbstract:A hallmark of adaptive humoral immunity is formation of germinal centers (GC), the site of B cell antigen-dependent clonal expansion, immunoglobulin diversification, and affinity maturation. This set of coordinated processes is dependent on follicular T cells and leads to generation of memory cells and long-lived plasma cells that secrete high-affinity antibodies. Despite the wealth of studies dissecting the chemotactic cues that organize GCs, it is unclear whether GC B cells may secrete additional factors that enable their efficient sampling by follicular T cells. In this work we show that in mice a small subset of GC Centrocytes upregulates expression of proinflammatory chemokines CCL3/4. We also demonstrate that GC B cells-intrinsic production of CCL3 promotes their direct interactions with follicular regulatory T cells (Tfr), but not follicular helper T cells (Tfh) in vivo . Finally, we show that GC B cells-intrinsic production of CCL3 is required for optimal control of GC responses.
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Video_1_CCL3 Promotes Germinal Center B Cells Sampling by Follicular Regulatory T Cells in Murine Lymph Nodes.MP4
2018Co-Authors: Zachary L. Benet, Matangi Marthi, Jackson S. Turner, Jahan B. Gabayre, Michael I. Ivanitskiy, Sahil S. Sethi, Irina L. GrigorovaAbstract:Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) Centrocytes. However, the role of CCL3/4 for Centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. Two-photon imaging revealed that B cells-intrinsic production of CCL3 promotes their probing by follicular regulatory T cells (Tfr) within GCs of murine lymph nodes. Overall this study suggests that CCL3 facilitates direct interactions of foreign antigen-specific GC B cells and their negative regulation with Tfr cells in vivo.
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Data_Sheet_1_CCL3 Promotes Germinal Center B Cells Sampling by Follicular Regulatory T Cells in Murine Lymph Nodes.PDF
2018Co-Authors: Zachary L. Benet, Matangi Marthi, Jackson S. Turner, Jahan B. Gabayre, Michael I. Ivanitskiy, Sahil S. Sethi, Irina L. GrigorovaAbstract:Previous studies and our findings suggest upregulated expression of proinflammatory chemokines CCL3/4 in germinal center (GC) Centrocytes. However, the role of CCL3/4 for Centrocyte interactions with follicular T cells and regulation of humoral immunity is poorly understood. We found that CCL3 promotes chemotaxis of Tfr cells ex vivo. Two-photon imaging revealed that B cells-intrinsic production of CCL3 promotes their probing by follicular regulatory T cells (Tfr) within GCs of murine lymph nodes. Overall this study suggests that CCL3 facilitates direct interactions of foreign antigen-specific GC B cells and their negative regulation with Tfr cells in vivo.
Peter G. Isaacson - One of the best experts on this subject based on the ideXlab platform.
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Follicular colonization in thyroid lymphoma.
The American journal of pathology, 1992Co-Authors: Peter G. Isaacson, Tim C Diss, Langxing Pan, A. Androulakis-papachristou, D H WrightAbstract:The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by Centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin-embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category.
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low grade gastric b cell lymphoma of mucosa associated lymphoid tissue malt a multifocal disease
Histopathology, 1992Co-Authors: A C Wotherspoon, Claudio Doglioni, Peter G. IsaacsonAbstract:Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic Centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.
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follicular colonization in b cell lymphoma of mucosa associated lymphoid tissue
The American Journal of Surgical Pathology, 1991Co-Authors: Peter G. Isaacson, Andrew Wotherspoon, Tim C Diss, Langxing PanAbstract:The formation of neoplastic B-cell follicles is universally accepted as diagnostic of a follicle centre cell (FCC) lymphoma. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are characterized by a diffuse infiltrate of cells of uncertain lineage known as "Centrocyte-like" cells because of their resemblance to Centrocytes (small cleaved cells). Some MALT lymphomas, however, contain numerous follicles and may even have a predominantly follicular appearance. These follicles may be reactive or show immunoglobulin (Ig) light-chain restriction, indicating their neoplastic nature. We have proposed that these neoplastic follicles are not composed of follicle centre cells but result from colonization of reactive follicles by CCL cells. In this study, the immunophenotype and genotype of 10 primary gastrointestinal lymphomas with a follicular component have been determined. One case exhibited the morphological, immunophenotypic, and genotypic features of FCC lymphoma (Ig light-chain restriction, CD10+, KB61 (CDw32)-, Jh, and bcl-2 gene rearrangement). Neoplastic follicles in the remaining nine cases, which showed the features of MALT lymphoma, were of a different phenotype (Ig light-chain restriction, CD10- KB61(CDw32)+), and these lymphomas showed Jh but not bcl-2 gene rearrangement. Taken in conjunction with the morphological features, these findings suggest that in these cases the neoplastic follicles formed as the result of colonization of previously reactive follicles by neoplastic CCL cells. Thus, not all lymphomas containing neoplastic follicles are of FCC origin. Follicular colonization, as seen in low-grade MALT lymphomas, is likely to be a recapitulation of an as yet undescribed normal immunological phenomenon that may involve marginal zone B cells.