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

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.

Bach2 is required for B cell and T cell memory differentiation

“…In the next part of their study, Shinnakasu et al investigate the molecular features of the memory commitment of B cells by transcriptomic analysis of GC B cells with high affinity for antigen (which are predisposed to differentiate into plasma cells) and low affinity for antigen (which are predisposed to develop into memory B cells) 1 . Focusing on genes specifically upregulated in the low-affinity compartment and previously linked to B cell differentiation, the authors identify Bach2 as a likely mediator of the memory B cell program.…”

“…Indeed, Shinnakasu et al show that Bach2 promotes the development of memory B cells independently of repression of Blimp-1 (ref. 1), but the precise mechanisms of this process remain to be elucidated.…”

“…volume 17 number 7 JulY 2016 nature immunology transgenic mouse model with GC B cell-specific expression of a tamoxifen-inducible transgene encoding Cre recombinase that allows fate mapping of GC B cell progeny 1 . With this elegant model, the authors study the development of memory B cells and investigate the molecular events that occur during this process.…”

“…While a large number of studies have elucidated the molecular machinery that drives the effector differentiation of lymphocytes, less is known about the transcriptional regulation of the development of memory B cells and T cells. In this issue of Nature Immunology, papers by Shinnakasu et al 1 and Roychoudhuri et al 2 identify the transcription factor Bach2 as a key regulator of the memory differentiation of lymphocytes in response to antigen and provide insight into the molecular mechanism of Bach2's activity in the lymphoid lineages (Fig. 1).…”

Somatic mutation-associated T follicular helper cell elevation in lung adenocarcinoma

“…Tfh also play an active role in facilitating differentiation of memory B cells – however, no increase in memory subsets was observed in tumour tissue in the BCCA cohort (Fig S2), possibly due to their migration to the periphery. 32 Recent reports have implicated IL-6 in germinal centre formation via increased differentiation of CD4 + T cells into a Tfh phenotype. 33 Given the pro- and anti-tumoural role of IL-6 in lung cancer, TLO formation may represent yet another function of this pleiotropic molecule through modulation of the tumour microenvironment as well as on tumour cells themselves.…”