Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138int B cells consisted of IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138int FO B cells was confirmed by attenuated Ca2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138int FO B cells was distinct from that of the CD138- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

中文翻译：

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CD138 的低水平表达标志着无能 B 细胞的自然产生。

自身反应性 B 细胞并没有被完全删除，但有些仍然是免疫活性或无反应性 B 细胞。虽然自身反应性 B 细胞作为无能细胞的持久性已在表达 B 细胞受体 (BCR) 对工程化自身抗原具有反应性的转基因小鼠模型中得到证实，但天然存在的无能 B 细胞的表征对于识别它们和了解它们的作用很重要对免疫调节或自身免疫性疾病的贡献。我们在此报告，脾脏 B 细胞中 CD138 的低水平表达标志着自然产生的无能 B 细胞，而不是浆细胞。CD138int B 细胞由 IgMlowIgDhigh 滤泡 (FO) B 细胞和稳态条件下的过渡 3 B 细胞组成。CD138int FO B 细胞表现出与表达工程化 BCR 的单克隆无反应性 B 细胞共享的无反应性基因表达谱，并且基因表达谱不同于浆细胞、年龄相关 B 细胞或生发中心 B 细胞。CD138int FO B 细胞的无能状态通过减弱的 Ca2+ 反应和在 BCR 与抗 IgM、抗 IgD、抗 Igκ 或抗 IgG 结合后未能上调 CD69 得到证实。CD138int FO B 细胞的 BCR 库不同于 CD138-FO B 细胞，包括一些具有低水平体细胞突变的类别转换 B 细胞。这些发现表明正常小鼠中存在多克隆无反应性 B 细胞，其特征是 CD138 低水平表达、IgM 下调、BCR 参与后 Ca2+ 和 CD69 反应降低，