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Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis 被引量:5
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作者 Anna-Karin E Palm Heike C Friedrich +3 位作者 Anja Mezger maya salomonsson Linda K Myers Sandra Kleinau 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2015年第4期493-503,共11页
Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have ex... Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis. We show that splenic marginal zone (MZ), but not B- 1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in na'='ve mice. Upon immunization with heterologous collagen II in complete Freund's adjuvant the collagen-reactive MZ B cells expanded rapidly, while the B-1 B cells showed a modest anti-collagen response. The MZ B cells were easily activated by toll-like receptor (TLR) 4 and 9-1igands in vitro, inducing proliferation and cytokine secretion, implying that dual engagement of the B-cell receptor and TLRs may promote the immune response to self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen-presenting capacity as reflected by cognate T-cell proliferation in vitroand induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient in complement receptors I and 2 demonstrated increased proliferation and cytokine production, while Fcy receptor lib deficiency of the cells lead to increased cytokine production and antigen presentation. In conclusion, our data highlight self-reactive MZ B cells as initiators of the autoimmune response in CIA, where complement and Fc receptors are relevant in controlling the self-reactivity in the cells. 展开更多
关键词 ARTHRITIS complement receptors Fc receptors marginal zone B cells mice
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