生物
免疫球蛋白D
免疫学
克隆缺失
抗体
抗原
克隆无能
幼稚B细胞
自身抗体
受体
作者
J. Andrew Duty,Peter Szodoray,Nai-Ying Zheng,Kristi A. Koelsch,Qingzhao Zhang,Mike Swiatkowski,Melissa Mathias,Lori Garman,Christina Helms,Britt Nakken,Kenneth J. Smith,A. Darise Farris,Patrick C. Wilson
摘要
Self-reactive B cells not controlled by receptor editing or clonal deletion may become anergic. We report that fully mature human B cells negative for surface IgM and retaining only IgD are autoreactive and functionally attenuated (referred to as naive IgD+IgM− B cells [BND]). These BND cells typically make up 2.5% of B cells in the peripheral blood, have antibody variable region genes in germline (unmutated) configuration, and, by all current measures, are fully mature. Analysis of 95 recombinant antibodies expressed from the variable genes of single BND cells demonstrated that they are predominantly autoreactive, binding to HEp-2 cell antigens and DNA. Upon B cell receptor cross-linkage, BND cells have a reduced capacity to mobilize intracellular calcium or phosphorylate tyrosines, demonstrating that they are anergic. However, intense stimulation causes BND cells to fully respond, suggesting that these cells could be the precursors of autoantibody secreting plasma cells in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. This is the first identification of a distinct mature human B cell subset that is naturally autoreactive and controlled by the tolerizing mechanism of functional anergy.
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