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Bim establishes the B cell repertoire from early to late in the immune response.

Int. Immunol.2020 Sep 05. Epub 2020 Sep 05
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摘要


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 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 VH 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.

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