Glia maturation factor-γis involved in S1P-induced marginal zone B-cell chemotaxis and optimal IgM production to type II T-independent antigen

Yingqian Li, Yue Tang, Jun Liu, Xin Meng, Ying Wang, Qing Min, Rongjian Hong, Takeshi Tsubata, Koji Hase, Ji Yang Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Marginal zone B cells (MZBs) represent a unique B-cell sub-population that rapidly differentiate into IgM-secreting plasma cells in response to T-independent (T-I) antigen. Sphingosine 1-phosphate (S1P) promotes MZB localization to the marginal zone. However, intracellular molecules involved in MZB localization and migration remain largely unknown. Here, we show that MZBs lacking the glia maturation factor-γ(GMFG) are impaired in chemotaxis toward S1P under both in vitro and in vivo conditions, suggesting that GMFG is an effector downstream of S1P receptors. GMFG undergoes serine phosphorylation upon S1P stimulation and is required for S1P-induced desensitization of S1P receptor 1 (S1PR1). Compared with wild-type mice, Gmfg-/- mice produce elevated levels of 4-hydroxy-3-nitrophenyl-acetyl (NP)-specific IgM against a T-I type II antigen, NP-Ficoll, accompanied by dysregulated MZB localization. These results identify GMFG as a regulator of S1P-induced MZB chemotaxis and reveal a role for MZB localization in the marginal zone for optimal IgM production against a T-I antigen.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalInternational immunology
Volume34
Issue number1
DOIs
Publication statusPublished - 2022 Jan 1

Keywords

  • B-cell migration
  • chemokine
  • immune response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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