Glia maturation factor-γ is involved in S1P-induced marginal zone B-cell chemotaxis and optimal IgM production to type II T-independent antigen. (21st October 2021)

• Record Type: Journal Article
• Authors: Li, Yingqian; Tang, Yue; Liu, Jun; Meng, Xin; Wang, Ying; Min, Qing; Hong, Rongjian; Tsubata, Takeshi; Hase, Koji; Wang, Ji-Yang
• Is Part Of: International immunology. Volume 34:Number 1(2022)
• Page Start: 35
• Page End: 43
• Publication Date: 2021-10-21
• Subjects: B-cell migration -- chemokine -- immune response; Immunology -- Periodicals; 616.079
• DOI: 10.1093/intimm/dxab097
• Languages: English
• ISSNs: 0953-8178

Abstract

Abstract : GMFG regulates MZB cell migration and T-I IgM production 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. Graphical abstract: