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

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 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.

Multi-Scale Modeling Recapitulates the Effect of Genetic Alterations Associated With Diffuse Large B-Cell Lymphoma in the Germinal Center Dynamics

“…Finally, there was a 42-fold higher PC than MCB production. Studies have shown the number of PCs and MBCs generated spleen and bone marrow during an immune response (Kishi et al, 2010;Weisel et al, 2016;Sugimoto-Ishige et al, 2020). Nevertheless, these numbers represent percentages of observed PCs and MBCs from the total number of splenic or bone marrow cells, which are not translatable to the number of output cells from a single GC and therefore are not directly comparable with our results.…”

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“…Finally, there was a 42-fold higher PC than MCB production. Studies have shown the number of PCs and MBCs generated spleen and bone marrow during an immune response (Kishi et al, 2010;Weisel et al, 2016;Sugimoto-Ishige et al, 2020). Nevertheless, these numbers represent percentages of observed PCs and MBCs from the total number of splenic or bone marrow cells, which are not translatable to the number of output cells from a single GC and therefore are not directly comparable with our results.…”