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Nicole Baumgarth - One of the best experts on this subject based on the ideXlab platform.
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tlr induces reorganization of the igm bcr complex regulating murine b 1 Cell responses to infections
eLife, 2019Co-Authors: Hannah P Savage, Kathrin Klasener, Fauna L Smith, Michael Reth, Nicole BaumgarthAbstract:In mice, neonatally-developing, self-reactive B-1 Cells generate steady levels of natural antibodies throughout life. B-1 Cells can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 Cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections of mice with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 Cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 Cells in immune defense via BCR-complex reorganization.
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tlr induced reorganization of the igm bcr complex regulates b 1 Cell responses to infections
bioRxiv, 2019Co-Authors: Hannah P Savage, Kathrin Klasener, Fauna L Smith, Michael Reth, Nicole BaumgarthAbstract:Abstract Neonatally-developing, self-reactive B-1 Cells generate steady levels natural antibodies throughout life. They can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 Cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 Cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 Cells in immune defense via BCR-complex reorganization.
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purification and immune phenotyping of b 1 Cells from body cavities of mice
Methods of Molecular Biology, 2014Co-Authors: Vanessa Yenson, Nicole BaumgarthAbstract:: B-1 Cells are innate-like lymphocytes that generate natural, polyreactive antibodies with important functions in tissue homeostasis and immune defense. While B-1-Cell frequencies in secondary lymphoid tissues are low, relative high frequencies are found within peritoneal and pleural cavities of mice, including both CD5(+) B-1a and CD5(-) B-1b Cells. They represent reservoirs of B-1 Cells that can be activated for migration to lymphoid tissues to secrete antibodies and/or cytokines. Here, we outline efficient methods for the extraction and magnetic isolation of B-1a Cells from the peritoneal and pleural cavities and the separation and phenotypic characterization of B-1a and B1-b Cells by flow cytometry.
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2000. B-1 and B-2 Cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection
2013Co-Authors: Nicole Baumgarth, Ometa C Herman, Gina C Jager, Lorena E Brown, Leonore A Herzenberg, Jianzhu ChenAbstract:We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 Cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 Cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 Cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 Cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 Cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 Cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 Cell–derived IgM antibodies as nonredundant components of the antiviral response. Key words: B Cells • immunoglobulin M • immune protection • CD5 � B Cell • respiratory trac
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The Journal of Experimental Medicine CORRESPONDENCE
2013Co-Authors: Youn Soo Choi, Nicole BaumgarthAbstract:receptor; BLF, BAL fluid; GC, germinal center; HI, hemagglutination inhibition; MedLN, mediastinal LN; PerC, peritoneal cavity wash out Cell; PLN, peripheral LN. B-1 Cells are known to contribute most of the “ natural antibodies ” that are secreted in the steady state, antibodies which are crucial for protection against many pathogens including influenza virus. Whether the CD5 + B-1a subset plays a role during an active immune response is incompletely understood. In contrast to recent data suggesting a passive role for B-1a Cells, data provided here show strong highly localized activation of B-1 Cells in the draining lymph nodes of the respiratory tract after influenza infection. B-1 Cells are identified as a major source for both steady state and infection-induced local virus-neutralizing IgM. The CD5 + B-1a subset is the main B-1 Cell subset generating this response. B-1a Cell responses are generated by their increased local accumulation rather than by antigenspecifi
Jianzhu Chen - One of the best experts on this subject based on the ideXlab platform.
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2000. B-1 and B-2 Cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection
2013Co-Authors: Nicole Baumgarth, Ometa C Herman, Gina C Jager, Lorena E Brown, Leonore A Herzenberg, Jianzhu ChenAbstract:We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 Cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 Cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 Cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 Cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 Cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 Cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 Cell–derived IgM antibodies as nonredundant components of the antiviral response. Key words: B Cells • immunoglobulin M • immune protection • CD5 � B Cell • respiratory trac
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2000. B-1 and B-2 Cell–derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection
2013Co-Authors: Nicole Baumgarth, Ometa C Herman, Gina C Jager, Lorena E Brown, Leonore A Herzenberg, Jianzhu ChenAbstract:We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 Cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 Cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 Cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 Cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 Cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 Cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 Cell–derived IgM antibodies as nonredundant components of the antiviral response. Key words: B Cells • immunoglobulin M • immune protection • CD5 � B Cell • respiratory trac
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b 1 and b 2 Cell derived immunoglobulin m antibodies are nonredundant components of the protective response to influenza virus infection
Journal of Experimental Medicine, 2000Co-Authors: Nicole Baumgarth, Ometa C Herman, Gina C Jager, Lorena E Brown, Leonore A Herzenberg, Jianzhu ChenAbstract:We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 Cell–derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 Cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 Cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 Cell–derived natural IgM is present before infection, whereas virus strain–specific, B-2 Cell–derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 Cell–derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 Cell–derived IgM antibodies as nonredundant components of the antiviral response.
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enhanced b 1 Cell development but impaired igg antibody responses in mice deficient in secreted igm
Journal of Immunology, 1998Co-Authors: Marianne Boes, Christine Esau, Michael B Fischer, Tara Schmidt, Michael C Carroll, Jianzhu ChenAbstract:The role of endogenous natural IgM in promoting the adaptive Ab response was investigated in newly constructed mutant mice in which B Cells do not secrete IgM but still express surface IgM and IgD and undergo class switching to express other Ig isotypes. While the mutant mice had relatively normal numbers of conventional B (B-2) Cells in all tissues examined, unexpectedly, B-1 Cells in the peritoneum and spleen were approximately threefold more abundant. The elevated levels of B-1 Cells were already detectable at 4 wk of age and were stably maintained throughout life. The levels of serum IgG2a, IgG3, and IgA were also elevated in the mutant mice at an early age. IgG2a response to a T Cell-independent Ag was augmented, whereas IgG Ab responses to suboptimal doses of a T Cell-dependent Ag were impaired. The latter defect was associated with fewer splenic germinal centers, impaired Ab affinity maturation, and less Ag trapping on follicular dendritic Cells. Together, these findings demonstrate a physiologic role of natural IgM in the feedback regulation of B-1 Cell development, the regulation of IgG2a production, and the promotion of efficient B-2 Cell Ab responses.
Jun-ichi Miyazaki - One of the best experts on this subject based on the ideXlab platform.
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defective b 1 Cell development and impaired immunity against angiostrongylus cantonensis in il 5rα deficient mice
Immunity, 1996Co-Authors: Toshimi Yoshida, Hiroko Sugaya, Kazushige Maki, Hiroko Kanazawa, Shinji Sunaga, Kentarou Yoshimura, Tatsuo Kinashi, M. Takagi, Koichi Ikuta, Jun-ichi MiyazakiAbstract:Abstract We generated interleukin-5 receptor α chain (IL-5Rα)–deficient (IL-5Rα −/− ) mice by gene targeting. The IL-5Rα −/− mice showed decreased numbers of B-1 Cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B Cell responses to T-independent antigens. The number of αβ T Cell receptor–positive thymocytes tended to decrease in 3-week-old IL-5Rα −/− mice, returning to normal by 6 weeks of age. The IL-5Rα −/− mice produced basal levels of eosinophils, while their bone marrow Cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5Rα −/− mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector Cells in the killing of Angiostrongylus cantonensis in mice.
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defective b 1 Cell development and impaired immunity against angiostrongylus cantonensis in il 5rα deficient mice
Immunity, 1996Co-Authors: Toshimi Yoshida, Hiroko Sugaya, Kazushige Maki, Hiroko Kanazawa, Shinji Sunaga, Kentarou Yoshimura, Tatsuo Kinashi, M. Takagi, Koichi Ikuta, Jun-ichi MiyazakiAbstract:We generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 Cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B Cell responses to T-independent antigens. The number of alpha beta T Cell receptor-positive thymocytes tended to decrease in 3-week-old IL-5R alpha-/- mice, returning to normal by 6 weeks of age. The IL-5R alpha-/- mice produced basal levels of eosinophils, while their bone marrow Cells failed to form eosinophilic colonies in response to IL-5. Impaired eosinophilopoiesis in IL-5R alpha-/-mice enhanced the survival of Angiostrongylus cantonensis. These results indicate that IL-5-induced eosinophils serve as potent effector Cells in the killing of Angiostrongylus cantonensis in mice.
Philip W Askenase - One of the best experts on this subject based on the ideXlab platform.
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invariant nkt Cells rapidly activated via immunization with diverse contact antigens collaborate in vitro with b 1 Cells to initiate contact sensitivity
Journal of Immunology, 2006Co-Authors: Regis A Campos, Marian Szczepanik, Atsuko Itakura, Maria Leitedemoraes, Mariette Lisbonne, Philip W AskenaseAbstract:In cutaneous contact sensitivity there is an early elicited innate cascade of complement, mast Cells, and platelets activated via IgM Abs. This response is required to initiate the elicitation of acquired classical contact sensitivity by leading to local recruitment of effector T Cells. We recently performed in vivo experiments showing that collaboration is required between innate-like invariant Vα14 + NKT Cells (iNKT) and the innate-like B-1 B Cell subset to induce this initiation process. Contact sensitization triggers iNKT Cells to produce IL-4 to coactivate the B-1 Cells along with specific Ag for production of the initiating IgM Abs. We now describe in vitro collaboration of iNKT and B-1 Cells. Normal peritoneal B-1 Cells, incubated in vitro with soluble Ag, and with 1-h in vivo immune iNKT Cells producing IL-4, are activated to mediate the contact sensitivity-initiation cascade. The three components of this process can be activated by different Ag. Thus, 1-h iNKT Cell activation, B-1 Cell stimulation, and generation of immune effector T Cells can be induced by sensitization with three different Ag to respectively generate IL-4 and Ag-specific IgM Abs, to recruit the Ag-specific effector T Cells. These findings have relevance to allergic and autoimmune diseases in which infections can trigger exacerbation of T Cell responses to allergens or to autoantigens.
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tlr dependent il 4 production by invariant vα14 jα18 nkt Cells to initiate contact sensitivity in vivo
Journal of Immunology, 2005Co-Authors: Philip W Askenase, Atsuko Itakura, Maria Leitedemoraes, Mariette Lisbonne, Sukit Roongapinun, Daniel R Goldstein, Marian SzczepanikAbstract:LPS stimulated B-1 Cell polyclonal in vivo IgM responses depend on IL-4 release by invariant Vα14 + Jα18 + NKT (iNKT) Cells. The IgM Abs can recruit effector T Cells to mediate contact sensitivity. LPS activates the B-1 Cell response just 1 day later, and depends on CD1d, iNKT Cells, IL-4, TLR4, and MyD88. LPS in vivo and in vitro stimulates rapid preferential production of IL-4 in hepatic iNKT Cells within 2 h. TLR4 were demonstrated in iNKT Cells by flow cytometry and functional studies. Thus, innate microbial stimulation via TLR can activate iNKT Cell and B-1 Cell collaboration. The result is polyclonal IgM Ab responses capable of recruiting Ag-specific T Cells into tissues. This may be involved in the promotion of autoimmunity by infectious agents.
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cutaneous immunization rapidly activates liver invariant vα14 nkt Cells stimulating b 1 b Cells to initiate t Cell recruitment for elicitation of contact sensitivity
Journal of Experimental Medicine, 2003Co-Authors: Marian Szczepanik, Atsuko Itakura, Regis A Campos, Moe Akahiraazuma, Stephane Sidobre, Mitchell Kronenberg, Philip W AskenaseAbstract:T Cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 Cells that produce IgM, which activates complement to promote T Cell passage into the tissues. We now show that Vα14i NKT Cells induce B-1 Cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT Cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT Cells. Transfers are not effective if Cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT Cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 Cells also reconstitutes CS responses in NKT Cell–deficient mice. The B-1 Cells act downstream of the Vα14i NKT Cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT Cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT Cells are stimulated to produce IL-4, which activates B-1 Cells to produce Ag-specific IgM, subsequently needed to recruit effector T Cells for elicitation of CS responses.
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b Cell dependent t Cell responses igm antibodies are required to elicit contact sensitivity
Journal of Experimental Medicine, 2002Co-Authors: Ryohei F Tsuji, Nicole Baumgarth, Ivana Kawikova, Vipin Paliwal, Marian Szczepanik, Atsuko Itakura, Regis A Campos, Leonore A Herzenberg, Moe Akahiraazuma, Philip W AskenaseAbstract:Contact sensitivity (CS) is a classic example of in vivo T Cell immunity in which skin sensitization with reactive hapten leads to immunized T Cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T Cell recruitment in CS is triggered by local activation of complement, which generates C5a that triggers C5a receptors most likely on mast Cells. Here, we show that B-1 Cell-derived antihapten IgM antibodies generated within 1 day (d) of immunization combine with local challenge antigen to activate complement to recruit the T Cells. These findings overturn three widely accepted immune response paradigms by showing that (a) specific IgM antibodies are required to initiate CS, which is a classical model of T Cell immunity thought exclusively due to T Cells, (b) CS priming induces production of specific IgM antibodies within 1 d, although primary antibody responses typically begin by day 4, and (c) B-1 Cells produce the 1-d IgM response to CS priming, although these Cells generally are thought to be nonresponsive to antigenic stimulation. Coupled with previous evidence, our findings indicate that the elicitation of CS is initiated by rapidly formed IgM antibodies. The IgM and challenge antigen likely form local complexes that activate complement, generating C5a, leading to local vascular activation to recruit the antigen-primed effector T Cells that mediate the CS response.
Regis A Campos - One of the best experts on this subject based on the ideXlab platform.
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invariant nkt Cells rapidly activated via immunization with diverse contact antigens collaborate in vitro with b 1 Cells to initiate contact sensitivity
Journal of Immunology, 2006Co-Authors: Regis A Campos, Marian Szczepanik, Atsuko Itakura, Maria Leitedemoraes, Mariette Lisbonne, Philip W AskenaseAbstract:In cutaneous contact sensitivity there is an early elicited innate cascade of complement, mast Cells, and platelets activated via IgM Abs. This response is required to initiate the elicitation of acquired classical contact sensitivity by leading to local recruitment of effector T Cells. We recently performed in vivo experiments showing that collaboration is required between innate-like invariant Vα14 + NKT Cells (iNKT) and the innate-like B-1 B Cell subset to induce this initiation process. Contact sensitization triggers iNKT Cells to produce IL-4 to coactivate the B-1 Cells along with specific Ag for production of the initiating IgM Abs. We now describe in vitro collaboration of iNKT and B-1 Cells. Normal peritoneal B-1 Cells, incubated in vitro with soluble Ag, and with 1-h in vivo immune iNKT Cells producing IL-4, are activated to mediate the contact sensitivity-initiation cascade. The three components of this process can be activated by different Ag. Thus, 1-h iNKT Cell activation, B-1 Cell stimulation, and generation of immune effector T Cells can be induced by sensitization with three different Ag to respectively generate IL-4 and Ag-specific IgM Abs, to recruit the Ag-specific effector T Cells. These findings have relevance to allergic and autoimmune diseases in which infections can trigger exacerbation of T Cell responses to allergens or to autoantigens.
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airway hyper reactivity mediated by b 1 Cell immunoglobulin m antibody generating complement c5a at 1 day post immunization in a murine hapten model of non atopic asthma
Immunology, 2004Co-Authors: Ivana Kawikova, Vipin Paliwal, Marian Szczepanik, Atsuko Itakura, Mieko Fukui, Regis A Campos, Gregory P Geba, Robert J Homer, Bettina P Iliopoulou, Jordan S PoberAbstract:Summary Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper-reactivity (AHR) to methacholine challenge, which is dependent on B Cells but not on T Cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naive recipients via 1-day immune Cells. Responses are absent in 1-day immune B-Cell-deficient JH−/− mice and B-1 B-Cell-deficient xid male mice, as well as in recipients of 1-day immune Cells depleted of Cells with the B-1 Cell phenotype (CD19+ B220+ CD5+). As B-1 Cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti-hapten IgM-producing Cells in the spleen and lymph nodes of 1-day immune wild-type mice, but not in xid mice. Then, we passively immunized naive mice with anti-hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor-deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B-1 Cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.
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cutaneous immunization rapidly activates liver invariant vα14 nkt Cells stimulating b 1 b Cells to initiate t Cell recruitment for elicitation of contact sensitivity
Journal of Experimental Medicine, 2003Co-Authors: Marian Szczepanik, Atsuko Itakura, Regis A Campos, Moe Akahiraazuma, Stephane Sidobre, Mitchell Kronenberg, Philip W AskenaseAbstract:T Cell recruitment to elicit contact sensitivity (CS) requires a CS-initiating process mediated by B-1 Cells that produce IgM, which activates complement to promote T Cell passage into the tissues. We now show that Vα14i NKT Cells induce B-1 Cell activation likely by releasing IL-4 early postimmunization. The CS initiation process is absent in Jα18−/− and CD1d−/− NKT Cell–deficient mice and is reconstituted by populations enriched for Vα14i NKT Cells. Transfers are not effective if Cells are derived from IL-4−/− mice. Staining with specific tetramers directly showed that hepatic Vα14i NKT Cells increase by 30 min and nearly double by 2 h postimmunization. Transfer of immune B-1 Cells also reconstitutes CS responses in NKT Cell–deficient mice. The B-1 Cells act downstream of the Vα14i NKT Cells to restore CS initiation. In addition, IL-4 given systemically to Jα18−/− or CD1d−/− NKT Cell–deficient mice reconstitutes elicitation of CS. Further, splenocytes from immune Jα18−/− mice produce less antigen (Ag)-specific IgM antibodies compared with sensitized WT mice. Together these findings indicate that very early after skin immunization Vα14i NKT Cells are stimulated to produce IL-4, which activates B-1 Cells to produce Ag-specific IgM, subsequently needed to recruit effector T Cells for elicitation of CS responses.
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b Cell dependent t Cell responses igm antibodies are required to elicit contact sensitivity
Journal of Experimental Medicine, 2002Co-Authors: Ryohei F Tsuji, Nicole Baumgarth, Ivana Kawikova, Vipin Paliwal, Marian Szczepanik, Atsuko Itakura, Regis A Campos, Leonore A Herzenberg, Moe Akahiraazuma, Philip W AskenaseAbstract:Contact sensitivity (CS) is a classic example of in vivo T Cell immunity in which skin sensitization with reactive hapten leads to immunized T Cells, which are then recruited locally to mediate antigen-specific inflammation after subsequent skin challenge. We have previously shown that T Cell recruitment in CS is triggered by local activation of complement, which generates C5a that triggers C5a receptors most likely on mast Cells. Here, we show that B-1 Cell-derived antihapten IgM antibodies generated within 1 day (d) of immunization combine with local challenge antigen to activate complement to recruit the T Cells. These findings overturn three widely accepted immune response paradigms by showing that (a) specific IgM antibodies are required to initiate CS, which is a classical model of T Cell immunity thought exclusively due to T Cells, (b) CS priming induces production of specific IgM antibodies within 1 d, although primary antibody responses typically begin by day 4, and (c) B-1 Cells produce the 1-d IgM response to CS priming, although these Cells generally are thought to be nonresponsive to antigenic stimulation. Coupled with previous evidence, our findings indicate that the elicitation of CS is initiated by rapidly formed IgM antibodies. The IgM and challenge antigen likely form local complexes that activate complement, generating C5a, leading to local vascular activation to recruit the antigen-primed effector T Cells that mediate the CS response.