Fig. 8
From: Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching of N-glycans
Proposed role of Gal-9 and I-branches in the regulation of BCR signaling in naive B cells vs. GC B cells. In naive B cells (right), Gal-9 is expressed at high levels and secreted into the microenvironment by an unconventional mechanism. Autologously, or exogenously, produced Gal-9 binds poly-LacNAc-containing N-glycans on CD45, which are predominantly of the linear type due to low expression of the I-branching glycosyltransferase GCNT2. Gal-9 binding to CD45 activates Lyn (by an undetermined mechanism), which subsequently phosphorylates tyrosine residues in CD22 ITIMs and recruits the protein tyrosine phosphatase SHP-1. SHP-1 phosphatase activity dampens cytoplasmic calcium levels, including calcium accumulation in response to BCR engagement, possibly through its reported ability to activate B cell calcium efflux pumps. Diminished intracellular calcium levels results in decreased nuclear translocation and activity of NFAT1 and other calcium sensitive signaling factors, ultimately inhibiting B cell activation. By contrast, Gal-9 activity is downmodulated in GC B cells (left) via the combined downregulation of Gal-9 protein and upregulation of GCNT2, which disfavors Gal-9 binding by modifying N-glycan poly-LacNAcs with I-branches
