Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction

Ihn Kyung Jang, Darran G. Cronshaw, Luo Kun Xie, Guoqiang Fang, Jinping Zhang, Hyunju Oh, Yang Xin Fu, Hua Gu, Yongrui Zou

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form germinal centers in the spleen after antigen stimulation. Furthermore, mutant mice exhibit defects in splenic architecture resembling that observed in B-cell-specific lymphotoxin-β- deficient mice, including disruption of marginal zone and follicular dendritic cell networks. We find that grb2-/- B cells are defective in lymphotoxin-β expression. Although lymphotoxin can be up-regulated by chemokine CXCL13 and CD40 ligand stimulation in wild-type B cells, elevation of lymphotoxin expression in grb2-/- B cells is only induced by anti-CD40 but not by CXCL13. Our results thus define Grb2 as a nonredundant regulator that controls lymphoid follicle organization and germinal center reaction. Loss of Grb2 has no effect on B-cell chemotaxis to CXCL13, indicating that Grb2 executes this function by connecting the CXCR5 signaling pathway to lymphotoxin expression but not to chemotaxis.

Original languageEnglish (US)
Pages (from-to)7926-7931
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number19
DOIs
StatePublished - May 10 2011

Keywords

  • B-cell signaling and activation
  • Chemokine signaling
  • Follicular dendritic cell development
  • Germinal center development
  • Regulation of lymphotoxin expression

ASJC Scopus subject areas

  • General

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