Abstract

In T cell-dependent antibody responses, some of the activated B cells differentiate along extrafollicular pathways into low-affinity memory and plasma cells, whereas others are involved in subsequent germinal center (GC) formation in follicular pathways, in which somatic hypermutation and affinity maturation occur. The present study demonstrated that Bim, a proapoptotic BH3-only member of the Bcl-2 family, contributes to the establishment of the B-cell repertoire from early to late stages of immune responses to T cell-dependent antigens. Extrafollicular plasma cells grew in the spleen during the early immune response, but their numbers rapidly declined with the appearance of GC-derived progeny in wild-type mice. By contrast, conditional Bim deficiency in B cells resulted in expansion of extrafollicular IgG1⁺ antibody-forming cells (AFCs) and this expansion was sustained during the late response, which hampered the formation of GC-derived high-affinity plasma cells in the spleen. Approximately 10% of AFCs in mutant mice contained mutated V_H genes; thus, Bim deficiency appears not to impede the selection of high-affinity AFC precursor cells. These results suggest that Bim contributes to the replacement of low-affinity antibody by high-affinity antibody as the immune response progresses.

中文翻译：

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Bim 在免疫反应的早期到晚期建立 B 细胞库

摘要

在 T 细胞依赖性抗体反应中，一些活化的 B 细胞沿滤泡外途径分化为低亲和力记忆细胞和浆细胞，而另一些则参与滤泡途径中随后的生发中心 (GC) 形成，其中体细胞超突变和亲和力成熟发生。本研究表明，Bim 是 Bcl-2 家族的仅促凋亡 BH3 成员，有助于建立从对 T 细胞依赖性抗原的免疫反应的早期到晚期的 B 细胞库。在早期免疫反应期间，滤泡外浆细胞在脾脏中生长，但随着野生型小鼠 GC 衍生后代的出现，它们的数量迅速下降。相比之下，B 细胞条件性 Bim 缺乏导致滤泡外 IgG1 ⁺抗体形成细胞 (AFC) 和这种扩张在晚期反应期间持续存在，这阻碍了脾脏中 GC 衍生的高亲和力浆细胞的形成。突变小鼠中大约 10% 的 AFC 含有突变的 V _H基因；因此，Bim 缺乏似乎不会阻碍高亲和力 AFC 前体细胞的选择。这些结果表明，随着免疫反应的进行，Bim 有助于用高亲和力抗体替代低亲和力抗体。