Regulated selection of germinal-center cells into the memory B cell compartment

R Shinnakasu, T Inoue, K Kometani, S Moriyama… - Nature …, 2016 - nature.com
R Shinnakasu, T Inoue, K Kometani, S Moriyama, Y Adachi, M Nakayama, Y Takahashi
Nature immunology, 2016nature.com
Despite the importance of memory B cells in protection from reinfection, how such memory
cells are selected and generated during germinal-center (GC) reactions remains unclear.
We found here that light-zone (LZ) GC B cells with B cell antigen receptors (BCRs) of lower
affinity were prone to enter the memory B cell pool. Mechanistically, cells in this memory-
prone fraction had higher expression of the transcriptional repressor Bach2 than that of their
counterparts with BCRs of higher affinity. Haploinsufficiency of Bach2 resulted in reduced …
Abstract
Despite the importance of memory B cells in protection from reinfection, how such memory cells are selected and generated during germinal-center (GC) reactions remains unclear. We found here that light-zone (LZ) GC B cells with B cell antigen receptors (BCRs) of lower affinity were prone to enter the memory B cell pool. Mechanistically, cells in this memory-prone fraction had higher expression of the transcriptional repressor Bach2 than that of their counterparts with BCRs of higher affinity. Haploinsufficiency of Bach2 resulted in reduced generation of memory B cells, independently of suppression of the gene encoding the transcription factor Blimp-1. Bach2 expression in GC cells was inversely correlated with the strength of help provided by T cells. Thus, we propose an instructive model in which weak help from T cells maintains relatively high expression of Bach2, which predisposes GC cells to enter the memory pool.
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