Depletion prior to collagen immunization results in reduced disease, as pathogenic

Depletion prior to collagen immunization results in reduced disease, as pathogenic autoantibodies can no longer drive autoimmune inflammation (52). Despite evidence that B cells are inflammatory mediators of autoimmunity during CIA, some B cells subsets have also been shown to negatively regulate antigen-specific immune responses during arthritic disease. Mauri et al. (53) have described that in vitro activation of B cells with agonistic CD40 mAb induces production of IL-10 and to a much lesser extent, IFN-. Transfer of these in vitro-activated B cells into collagen-immunized DBA/1 with transgenic T-cell receptors specific for collagen significantly delayed Cyclopamine manufacturer disease onset and ameliorated established disease. The observed effects were attributed to the ability of the transferred B cells to produce IL-10, as B cells derived from IL-10-/- mice were without effect. An immunosuppressive role for B cells during CIA was further described in studies where the CD21hi CD23+ IgM+ transitional 2 marginal zone precursor (T2-MZP) cell population was isolated and transferred to collagen-immunized DBA/1 mice (54). TZ-MZP cell adoptive transfers delayed disease onset and treated established disease via inhibition of Th1-type immune responses in an IL-10-dependent manner. Moreover, adoptive transfer of total splenic B cells from apoptotic cell-treated mice also suppressed autoimmune pathogenesis in an IL-10-dependent manner that encouraged CD4+ T cell IL-10 production, thus verifying the ability of particular B-cell subsets to instigate tolerance and inhibit arthritic inflammation in CIA (22). A role for B10 cells specifically during CIA was investigated by Yang et al. using B cells cultured in vitro with BAFF for 72 h, which is reported to induce IL-10 production in approximately 32 of CD1dhi CD5+ B cells (55). The B10 cell-enriched B cells were then transferred to collagen-immunized DBA/1 mice where they delayed the onset of arthritis and specifically downregulated Th17 responses. Taken together, these studies confirmed the role of B cells during CIA and documented that while some pathogenic B-cell populations certainly contribute to the progression of disease, regulatory B-cell subsets, especially B10 cells, are capable of inhibiting effector T-cell responses during the course of CIA.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptImmunol Rev. Author manuscript; available in PMC 2015 May 01.Candando et al.PageB10 cell regulation of Crotaline biological activity pathogen clearance Unlike autoimmune models in which B10 cells ameliorate disease and improve symptoms, the presence of B10 cells during infection prevents efficient pathogen clearance. During Listeria monocytogenes infection, antibody-mediated B10 cell depletion resulted in reduced bacterial load and enhanced macrophage activity (29). Although B10 cells inhibited innate cells in this model, their regulatory effects were nonetheless dependent upon cognate interactions with T cells, as B10 cells deficient in MHC-II or IL-21R did not affect Listeria responses. These findings clearly document a role for B10 cells in regulating immune system homeostasis, whereby the presence of B10 cells establishes the normal course of pathogen clearance. Remarkably, the depletion of B10 cells thereby enhances immunity and accelerates pathogen clearance. Regulatory B cells have also been implicated in suppression of immune responses during Salmonella typhimurium infection. In this study, B-cell-deficient mice reconsti.Depletion prior to collagen immunization results in reduced disease, as pathogenic autoantibodies can no longer drive autoimmune inflammation (52). Despite evidence that B cells are inflammatory mediators of autoimmunity during CIA, some B cells subsets have also been shown to negatively regulate antigen-specific immune responses during arthritic disease. Mauri et al. (53) have described that in vitro activation of B cells with agonistic CD40 mAb induces production of IL-10 and to a much lesser extent, IFN-. Transfer of these in vitro-activated B cells into collagen-immunized DBA/1 with transgenic T-cell receptors specific for collagen significantly delayed disease onset and ameliorated established disease. The observed effects were attributed to the ability of the transferred B cells to produce IL-10, as B cells derived from IL-10-/- mice were without effect. An immunosuppressive role for B cells during CIA was further described in studies where the CD21hi CD23+ IgM+ transitional 2 marginal zone precursor (T2-MZP) cell population was isolated and transferred to collagen-immunized DBA/1 mice (54). TZ-MZP cell adoptive transfers delayed disease onset and treated established disease via inhibition of Th1-type immune responses in an IL-10-dependent manner. Moreover, adoptive transfer of total splenic B cells from apoptotic cell-treated mice also suppressed autoimmune pathogenesis in an IL-10-dependent manner that encouraged CD4+ T cell IL-10 production, thus verifying the ability of particular B-cell subsets to instigate tolerance and inhibit arthritic inflammation in CIA (22). A role for B10 cells specifically during CIA was investigated by Yang et al. using B cells cultured in vitro with BAFF for 72 h, which is reported to induce IL-10 production in approximately 32 of CD1dhi CD5+ B cells (55). The B10 cell-enriched B cells were then transferred to collagen-immunized DBA/1 mice where they delayed the onset of arthritis and specifically downregulated Th17 responses. Taken together, these studies confirmed the role of B cells during CIA and documented that while some pathogenic B-cell populations certainly contribute to the progression of disease, regulatory B-cell subsets, especially B10 cells, are capable of inhibiting effector T-cell responses during the course of CIA.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptImmunol Rev. Author manuscript; available in PMC 2015 May 01.Candando et al.PageB10 cell regulation of pathogen clearance Unlike autoimmune models in which B10 cells ameliorate disease and improve symptoms, the presence of B10 cells during infection prevents efficient pathogen clearance. During Listeria monocytogenes infection, antibody-mediated B10 cell depletion resulted in reduced bacterial load and enhanced macrophage activity (29). Although B10 cells inhibited innate cells in this model, their regulatory effects were nonetheless dependent upon cognate interactions with T cells, as B10 cells deficient in MHC-II or IL-21R did not affect Listeria responses. These findings clearly document a role for B10 cells in regulating immune system homeostasis, whereby the presence of B10 cells establishes the normal course of pathogen clearance. Remarkably, the depletion of B10 cells thereby enhances immunity and accelerates pathogen clearance. Regulatory B cells have also been implicated in suppression of immune responses during Salmonella typhimurium infection. In this study, B-cell-deficient mice reconsti.

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