The Experts below are selected from a list of 279 Experts worldwide ranked by ideXlab platform
Susan K. Pierce - One of the best experts on this subject based on the ideXlab platform.
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Viewing the antigen-induced initiation of B-Cell Activation in living Cells.
Immunological reviews, 2008Co-Authors: Pavel Tolar, Hae Won Sohn, Susan K. PierceAbstract:The Binding of antigen to the B-Cell receptor (BCR) induces BCR clustering and signaling cascades that lead to the Activation of a variety of genes associated with B-Cell Activation. Over the last several years, our understanding of the molecular details of the BCR signaling pathways have Been consideraBly advanced; what remains only poorly understood are the molecular events that initiate BCR clustering and how clustering leads to Activation. Here, we review our progress using live Cell imaging technologies to view the earliest events that follow the B Cell's Binding of antigen. We provide a model for BCR clustering and B-Cell Activation that involves an intrinsic tendency of the BCR to cluster and does not require direct crosslinking of the BCR By multivalent antigens. We suggest that local memBrane topology and lipid composition play key roles in BCR clustering and initiation of signaling. We Believe that our model for B-Cell Activation, in which receptor interactions with monovalent antigens on memBrane surfaces lead to receptor clustering, may Be highly relevant to the mechanisms By which other immune receptors cluster including the T-Cell receptor in response to monovalent peptide-major histocompatiBility complex complexes.
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Lipid rafts and B-Cell Activation.
Nature Reviews Immunology, 2002Co-Authors: Susan K. PierceAbstract:The B-Cell antigen receptor acts during B-Cell Activation Both to initiate signalling cascades and to transport antigen into the Cell for suBsequent processing and presentation. Recent evidence indicates that memBrane microdomains, termed lipid rafts, have a role in B-Cell Activation as platforms for B-Cell receptor (BCR) signalling and might also act in antigen trafficking. Lipid rafts might facilitate the regulation of the BCR during B-Cell development By B-Cell co-receptors, and during viral infection. So, lipid rafts seem to Be an important new piece of the B-Cell signalling puzzle.
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Lipid rafts and B-Cell Activation
Nature Reviews Immunology, 2002Co-Authors: Susan K. PierceAbstract:The B-Cell antigen receptor acts during B-Cell Activation Both to initiate signalling cascades and to transport antigen into the Cell for suBsequent processing and presentation. Recent evidence indicates that memBrane microdomains, termed lipid rafts, have a role in B-Cell Activation as platforms for B-Cell receptor (BCR) signalling and might also act in antigen trafficking. Lipid rafts might facilitate the regulation of the BCR during B-Cell development By B-Cell co-receptors, and during viral infection. So, lipid rafts seem to Be an important new piece of the B-Cell signalling puzzle. Lipid rafts act as platforms in B Cells for B-Cell receptor (BCR) signalling and antigen targeting. Rafts concentrate the Src-family kinase Lyn and exclude the BCR and receptors that negatively regulate BCR signalling. BCR oligomerization results in association of the BCR with lipid rafts and its phosphorylation By Lyn, initiating signalling. The association of the BCR with lipid rafts changes during B-Cell development, which might contriBute to the differences in the outcome of antigen encounter. B-Cell co-receptors, including CD19–CD21 and FcγRII influence the association of the BCR with rafts, which might represent a new mechanism for co-receptor function. Epstein–Barr-virus-encoded gene products LMP1 and LMP2A are constitutively associated with rafts and act within rafts to Block BCR signalling, providing signals for longevity and inducing latency.
Facundo D. Batista - One of the best experts on this subject based on the ideXlab platform.
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The Cytoskeleton Coordinates the Early Events of B-Cell Activation
Cold Spring Harbor perspectives in biology, 2011Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:B Cells contriBute to protective adaptive immune responses through generation of antiBodies and long-lived memory Cells, following engagement of the B-Cell receptor (BCR) with specific antigen. Recent imaging investigations have offered novel insights into the ensuing molecular and Cellular events underlying B-Cell Activation. Following engagement with antigen, BCR microclusters form and act as sites of active signaling through the recruitment of intraCellular signaling molecules and adaptors. Signaling through these “microsignalosomes” is propagated and enhanced through B-Cell spreading in a CD19-dependent manner. SuBsequently, the mature immunological synapse is formed, and functions as a platform for antigen internalization, enaBling the antigen presentation to helper T Cells required for maximal B-Cell Activation. In this review, we discuss the emerging and critical role for the cytoskeleton in the coordination and regulation of these molecular events during B-Cell Activation.
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Visualizing a role for the actin cytoskeleton in the regulation of B-Cell Activation.
Immunological reviews, 2010Co-Authors: Facundo D. Batista, Bebhinn Treanor, Naomi E. HarwoodAbstract:Appropriate Activation of B Cells is required for mounting protective humoral immune responses. B-Cell Activation is initiated following specific recognition of antigen By the B-Cell receptor (BCR) and results in the generation of antiBody-secreting plasma Cells and long-lived memory Cells. Initial imaging approaches revealed that B Cells undergo dramatic molecular and morphological reorganizations following recognition of antigen. A numBer of these studies pointed to a role for the underlying cytoskeleton in regulating early events of B-Cell Activation. More recently, groundBreaking advances in imaging technologies have enaBled direct visualization of the role for the cytoskeleton in regulating events at the B-Cell memBrane. Indeed, we have demonstrated that an ezrin-defined actin network shapes BCR diffusion and signaling Both in the resting state and following antigen-induced Activation. Importantly, alongside these in vitro imaging approaches, it has Been demonstrated that mutations in cytoskeleton regulators such as CD19, dedicator of cytokinesis 8 (DOCK8), and Wiskott-Aldrich syndrome protein (WASp) are often associated with antiBody deficiency syndromes in humans, estaBlishing the importance of cytoskeleton reorganizations in conferring effective adaptive immunity.
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Early Events in B Cell Activation
Annual review of immunology, 2010Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:B Cell Activation is initiated By the ligation of the B Cell receptor (BCR) with antigen and ultimately results in the production of protective antiBodies against potentially pathogenic invaders. Here we review recent literature concerned with the spatiotemporal dynamic characterization of the early molecular events of B Cell Activation, including the initiation of BCR triggering, the formation of BCR microclusters, and the dynamic regulation of BCR signaling. Because these events involve the consideraBle reorganization of molecules within the memBrane, an important role for the cytoskeleton is emerging in the regulation of B Cell Activation. At each stage we highlight the role of the cytoskeleton, estaBlishing its pivotal position during the initiation and regulation of B Cell Activation.
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Early events of B Cell Activation By antigen.
Science signaling, 2009Co-Authors: David Depoil, Yolanda R. Carrasco, Naomi E. Harwood, Michele Weber, Bebhinn Treanor, Sebastian J. Fleire, Facundo D. BatistaAbstract:The Activation of B Cells confers long-lasting protection from a plethora of infectious diseases through the generation of plasma Cells that produce high-affinity antiBodies and memory Cells. Engagement of the B Cell receptor (BCR) with cognate antigen initiates intraCellular signaling and suBsequent internalization of antigen. MemBrane-Bound antigens are now considered the predominant forms that initiate B Cell Activation in vivo. We have shown that upon recognition of antigen on the surface of a presenting Cell, the B Cell undergoes a dramatic change in morphology characterized By rapid spreading followed By more prolonged contraction along the presenting surface. This two-phase response increases the amount of antigen that the B Cell accumulates, internalizes, and suBsequently presents to T Cells. Thus, the spreading and contraction response shapes the outcome of B Cell Activation. We used a comBination of planar lipid Bilayers and total internal reflection fluorescence microscopy to investigate the early events that occur after engagement of the BCR and Before B Cell spreading. We oBserved the rapid formation of BCR-antigen microclusters, which we redefine as "microsignalosomes" Because they mediate the coordinated recruitment of intraCellular effectors, such as the kinases Lyn and Syk, the adaptor Vav, and phospholipase C-gamma2 (PLC-gamma2). We identified an essential role for the co-receptor CD19 in mediating spreading, and thus B Cell Activation, in response to memBrane-Bound antigen. Preliminary evidence suggests that the Cellular morphology changes descriBed in vitro are likely to occur upon recognition of antigen presented on the surface of macrophages in lymph nodes in vivo.
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New insights into the early molecular events underlying B Cell Activation.
Immunity, 2008Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:The appropriate Activation of B Cells is critical for the development and operation of immune responses and is dependent on the extensive coordination of intra- and interCellular communications in response to antigen stimulation. An accurate description of the B Cell-Activation process requires investigation of these interactions within their correct Cellular context Both at high resolution and in real time. Here, we discuss a numBer of recent studies that have offered insight into the early molecular events of B Cell Activation. We suggest that segregation within the B Cell memBrane triggers localized cytoskeleton reorganisation and signaling, allowing the formation of B Cell receptor (BCR) microclusters. These BCR microclusters are the sites for the coordinated recruitment of the signalosome and are propagated during B Cell spreading. We discuss the recent identification of a critical role for CD19 in the B Cell response to memBrane-Bound antigen and suggest a mechanism involving BCR microclusters By which it mediates its stimulatory function. Finally, we consider research that has taken advantage of recent technological advances in multiphoton microscopy that have allowed its application to the investigation of the dynamics of memBrane-Bound antigen presentation and suBsequent B Cell Activation in lymph nodes in vivo.
Hans Achaorbea - One of the best experts on this subject based on the ideXlab platform.
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dominant role of cd80 cd86 over cd40 and icosl in the massive polyclonal B Cell Activation mediated By laty136f cd4 t Cells
Frontiers in Immunology, 2012Co-Authors: Stephane Chevrier, Celine Genton, Bernard Malissen, Marie Malissen, Hans AchaorbeaAbstract:Coordinated interactions Between T and B Cells are crucial for inducing physiological B Cell responses. Mutant mice in which tyrosine 136 of LAT is replaced By a phenylalanine (LatY136F) exhiBit a strong CD4+ T Cell proliferation in the aBsence of intended immunization. The resulting effector T Cells produce high amounts of TH2 cytokines and are extremely efficient at inducing polyclonal B Cell Activation. As a consequence, these LatY136F mutant mice showed massive germinal centre formations and hypergammagloBulinemia. Here, we analyzed the involvement of different costimulators and their ligands in such T-B interactions Both in vitro and in vivo, using Blocking antiBodies, knockout mice and adoptive transfer experiments. Surprisingly, we showed in vitro that although B Cell Activation required contact with T Cells, CD40 and ICOSL signalling were not necessary for this process. These oBservations were further confirmed in vivo, where none of these molecules were required for the unfolding of the LAT CD4+ T Cell expansion and the suBsequent polyclonal B Cell Activation, although, the aBsence of CD40 led to a reduction of the follicular B Cell response. These results indicate that the crucial functions played By CD40 and ICOSL in germinal centre formation and isotype switching in physiological humoral responses are partly overcome in LatY136F mice. By comparison, the aBsence of CD80-CD86 was found to almost completely Block the in vitro B Cell Activation mediated By LatY136F CD4+ T Cells. The role of CD80-CD86 in T-B cooperation in vivo remained elusive due to the upstream implication of these costimulatory molecules in the expansion of LatY136F CD4+ T Cells. Together, our data suggest that CD80 and CD86 costimulators play a key role in the polyclonal B Cell Activation mediated By LatY136F CD4+ T Cells even though additional costimulatory molecules or cytokines are likely to Be required in this process.
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the th2 lymphoproliferation developing in laty136f mutant mice triggers polyclonal B Cell Activation and systemic autoimmunity
Journal of Immunology, 2006Co-Authors: Celine Genton, Bernard Malissen, Marie Malissen, Ying Wang, Shozo Izui, Georges Delsol, Gilbert J Fournie, Hans AchaorbeaAbstract:Lat(Y136F) knock-in mice harBor a point mutation in Tyr(136) of the linker for Activation of T Cells and show accumulation of Th2 effector Cells and IgG1 and IgE hypergammagloBulinemia. B Cell Activation is not a direct effect of the mutation on B Cells since in the aBsence of T Cells, mutant B Cells do not show an activated phenotype. After adoptive transfer of linker for Activation of T Cell mutant T Cells into wild-type, T Cell-deficient recipients, recipient B Cells Become activated. We show in vivo and in vitro that the Lat(Y136F) mutation promotes T Cell-dependent B Cell Activation leading to germinal center, memory, and plasma Cell formation even in an MHC class II-independent manner. All the plasma and memory B Cell populations found in physiological T Cell-dependent B Cell responses are found. Characterization of the aBundant plasmaBlasts found in secondary lymphoid organs of Lat(Y136F) mice revealed the presence of a previously uncharacterized CD93-expressing suBpopulation, whose presence was confirmed in wild-type mice after immunization. In Lat(Y136F) mice, B Cell Activation was polyclonal and not Ag-driven Because the increase in serum IgG1 and IgE concentrations involved ABs and autoantiBodies with different specificities equally. Although the noncomplement-fixing IgG1 and IgE are the only isotypes significantly increased in Lat(Y136F) serum, we oBserved early-onset systemic autoimmunity with nephritis showing IgE autoantiBody deposits and severe proteinuria. These results show that Th2 Cells developing in Lat(Y136F) mice can trigger polyclonal B Cell Activation and thereBy lead to systemic autoimmune disease.
Naomi E. Harwood - One of the best experts on this subject based on the ideXlab platform.
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The Cytoskeleton Coordinates the Early Events of B-Cell Activation
Cold Spring Harbor perspectives in biology, 2011Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:B Cells contriBute to protective adaptive immune responses through generation of antiBodies and long-lived memory Cells, following engagement of the B-Cell receptor (BCR) with specific antigen. Recent imaging investigations have offered novel insights into the ensuing molecular and Cellular events underlying B-Cell Activation. Following engagement with antigen, BCR microclusters form and act as sites of active signaling through the recruitment of intraCellular signaling molecules and adaptors. Signaling through these “microsignalosomes” is propagated and enhanced through B-Cell spreading in a CD19-dependent manner. SuBsequently, the mature immunological synapse is formed, and functions as a platform for antigen internalization, enaBling the antigen presentation to helper T Cells required for maximal B-Cell Activation. In this review, we discuss the emerging and critical role for the cytoskeleton in the coordination and regulation of these molecular events during B-Cell Activation.
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Visualizing a role for the actin cytoskeleton in the regulation of B-Cell Activation.
Immunological reviews, 2010Co-Authors: Facundo D. Batista, Bebhinn Treanor, Naomi E. HarwoodAbstract:Appropriate Activation of B Cells is required for mounting protective humoral immune responses. B-Cell Activation is initiated following specific recognition of antigen By the B-Cell receptor (BCR) and results in the generation of antiBody-secreting plasma Cells and long-lived memory Cells. Initial imaging approaches revealed that B Cells undergo dramatic molecular and morphological reorganizations following recognition of antigen. A numBer of these studies pointed to a role for the underlying cytoskeleton in regulating early events of B-Cell Activation. More recently, groundBreaking advances in imaging technologies have enaBled direct visualization of the role for the cytoskeleton in regulating events at the B-Cell memBrane. Indeed, we have demonstrated that an ezrin-defined actin network shapes BCR diffusion and signaling Both in the resting state and following antigen-induced Activation. Importantly, alongside these in vitro imaging approaches, it has Been demonstrated that mutations in cytoskeleton regulators such as CD19, dedicator of cytokinesis 8 (DOCK8), and Wiskott-Aldrich syndrome protein (WASp) are often associated with antiBody deficiency syndromes in humans, estaBlishing the importance of cytoskeleton reorganizations in conferring effective adaptive immunity.
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Early Events in B Cell Activation
Annual review of immunology, 2010Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:B Cell Activation is initiated By the ligation of the B Cell receptor (BCR) with antigen and ultimately results in the production of protective antiBodies against potentially pathogenic invaders. Here we review recent literature concerned with the spatiotemporal dynamic characterization of the early molecular events of B Cell Activation, including the initiation of BCR triggering, the formation of BCR microclusters, and the dynamic regulation of BCR signaling. Because these events involve the consideraBle reorganization of molecules within the memBrane, an important role for the cytoskeleton is emerging in the regulation of B Cell Activation. At each stage we highlight the role of the cytoskeleton, estaBlishing its pivotal position during the initiation and regulation of B Cell Activation.
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Early events of B Cell Activation By antigen.
Science signaling, 2009Co-Authors: David Depoil, Yolanda R. Carrasco, Naomi E. Harwood, Michele Weber, Bebhinn Treanor, Sebastian J. Fleire, Facundo D. BatistaAbstract:The Activation of B Cells confers long-lasting protection from a plethora of infectious diseases through the generation of plasma Cells that produce high-affinity antiBodies and memory Cells. Engagement of the B Cell receptor (BCR) with cognate antigen initiates intraCellular signaling and suBsequent internalization of antigen. MemBrane-Bound antigens are now considered the predominant forms that initiate B Cell Activation in vivo. We have shown that upon recognition of antigen on the surface of a presenting Cell, the B Cell undergoes a dramatic change in morphology characterized By rapid spreading followed By more prolonged contraction along the presenting surface. This two-phase response increases the amount of antigen that the B Cell accumulates, internalizes, and suBsequently presents to T Cells. Thus, the spreading and contraction response shapes the outcome of B Cell Activation. We used a comBination of planar lipid Bilayers and total internal reflection fluorescence microscopy to investigate the early events that occur after engagement of the BCR and Before B Cell spreading. We oBserved the rapid formation of BCR-antigen microclusters, which we redefine as "microsignalosomes" Because they mediate the coordinated recruitment of intraCellular effectors, such as the kinases Lyn and Syk, the adaptor Vav, and phospholipase C-gamma2 (PLC-gamma2). We identified an essential role for the co-receptor CD19 in mediating spreading, and thus B Cell Activation, in response to memBrane-Bound antigen. Preliminary evidence suggests that the Cellular morphology changes descriBed in vitro are likely to occur upon recognition of antigen presented on the surface of macrophages in lymph nodes in vivo.
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New insights into the early molecular events underlying B Cell Activation.
Immunity, 2008Co-Authors: Naomi E. Harwood, Facundo D. BatistaAbstract:The appropriate Activation of B Cells is critical for the development and operation of immune responses and is dependent on the extensive coordination of intra- and interCellular communications in response to antigen stimulation. An accurate description of the B Cell-Activation process requires investigation of these interactions within their correct Cellular context Both at high resolution and in real time. Here, we discuss a numBer of recent studies that have offered insight into the early molecular events of B Cell Activation. We suggest that segregation within the B Cell memBrane triggers localized cytoskeleton reorganisation and signaling, allowing the formation of B Cell receptor (BCR) microclusters. These BCR microclusters are the sites for the coordinated recruitment of the signalosome and are propagated during B Cell spreading. We discuss the recent identification of a critical role for CD19 in the B Cell response to memBrane-Bound antigen and suggest a mechanism involving BCR microclusters By which it mediates its stimulatory function. Finally, we consider research that has taken advantage of recent technological advances in multiphoton microscopy that have allowed its application to the investigation of the dynamics of memBrane-Bound antigen presentation and suBsequent B Cell Activation in lymph nodes in vivo.
Adriana Gruppi - One of the best experts on this subject based on the ideXlab platform.
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polyclonal B Cell Activation in infections infectious agents devilry or defense mechanism of the host
Journal of Leukocyte Biology, 2007Co-Authors: Carolina L. Montes, Eva V Acostarodriguez, Maria C Merino, Daniela A Bermejo, Adriana GruppiAbstract:Polyclonal B Cell Activation is not a pe- culiar characteristic to a particular infection, as many viruses, Bacteria, and parasites induce a strong polyclonal B Cell response resulting in hy- per--gloBulinemia. Here, we discuss the different roles proposed for polyclonal B Cell Activation, which can Be crucial for early host defense against rapidly dividing microorganisms By contriButing antiBodies specific for a spectrum of conserved structures present in the pathogens. In addition, polyclonal B Cell Activation can Be responsiBle for maintenance of memory B Cell responses Because of the continuous, unrestricted stimulation of memory B Cells whose antiBody production may Be sustained in the aBsence of the antigens Binding- specific BCR. Conversely, polyclonal Activation can Be triggered By microorganisms to avoid the host- specific, immune response By activating B Cell clones, which produce nonmicroorganism-specific antiBod- ies. Finally, some reports suggest a deleterious role for polyclonal Activation, arguing that it could poten- tially turn on anti-self-responses and lead to autoim- mune manifestations during chronic infections. J. Leukoc. Biol. 82: 1027-1032; 2007.
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Polyclonal B Cell Activation in infections: infectious agents devilry or defense mechanism of the host?
Journal of leukocyte biology, 2007Co-Authors: Carolina L. Montes, Maria C Merino, Daniela A Bermejo, Eva V. Acosta-rodríguez, Adriana GruppiAbstract:Polyclonal B Cell Activation is not a peculiar characteristic to a particular infection, as many viruses, Bacteria, and parasites induce a strong polyclonal B Cell response resulting in hyper-gamma-gloBulinemia. Here, we discuss the different roles proposed for polyclonal B Cell Activation, which can Be crucial for early host defense against rapidly dividing microorganisms By contriButing antiBodies specific for a spectrum of conserved structures present in the pathogens. In addition, polyclonal B Cell Activation can Be responsiBle for maintenance of memory B Cell responses Because of the continuous, unrestricted stimulation of memory B Cells whose antiBody production may Be sustained in the aBsence of the antigens Binding-specific BCR. Conversely, polyclonal Activation can Be triggered By microorganisms to avoid the host-specific, immune response By activating B Cell clones, which produce nonmicroorganism-specific antiBodies. Finally, some reports suggest a deleterious role for polyclonal Activation, arguing that it could potentially turn on anti-self-responses and lead to autoimmune manifestations during chronic infections.
