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

Nat Immunol. 2016 Jul;17(7):861-9. doi: 10.1038/ni.3460. Epub 2016 May 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / physiology*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • Germinal Center / immunology*
  • Immunologic Memory*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Positive Regulatory Domain I-Binding Factor 1
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Bach2 protein, mouse
  • Basic-Leucine Zipper Transcription Factors
  • Prdm1 protein, mouse
  • Receptors, Antigen, B-Cell
  • Transcription Factors
  • Positive Regulatory Domain I-Binding Factor 1