B cell glycosylation modulates mucosal immunity in experimental models of colitis

CUTINE AM; CAGNONI AJ; GATTO S; TOSCANO MA; MANSELLE COCCO MN; MORALES R; RABINOVICH GA; MOROSI L; MARTINEZ ALLO V; MAY M; MARIÑO KV

Simposio; GlycoAr 2019, Argentinian Glycobiology Symposium; 2019

The glycome of immune cells is a key regulator of cellular processes relevant to health anddisease. It has been shown that development of intestinal inflammation alters T cellglycosylation, contributing to the exacerbation of inflammatory bowel diseases (IBD).However, the glycome of other immune cells during colitis remains poorly described. Here,we demonstrate that chronic inflammation alters glycosylation in both B lymphocytes andplasma cells, negatively affecting their tolerogenic role during colitis. Our results show thatthe glycome of colonic B cells and IgA + plasma cells (PCs) from mice coursing DSS-induced chronic colitis presented lower levels of surface α2,6-sialylation (α2,6sia). Thus,we examined the lack of α2,6sia in either WT or ST6Gal1 deficient animals (ST6Gal1 -/- ), aglycosyltransferase that adds α2,6sia to N-glycans. ST6Gal1 -/- mice develop more severedisease signs and inflammatory score as a result of DSS colitis. To investigate the role ofα2,6sia specifically on B cells, we co-transferred into RAG2 -/- mice colitogenic-CD4 + CD45RB hi T cells with B cells isolated from either WT or ST6Gal1 -/- mice. While co-transfer with WT B cells reduced colonic T cell infiltration, co-transferring with ST6Gal1 -/- Bcells resulted in higher inflammation, and lower amounts of both fecal IgA and PCs whencompared to WT B cells. Collectively, our results suggest that α2,6sia exerts a regulatoryrole on B cells during IBD and provide a potential mechanism for the modulation of B cellfunctionality on inflamed intestinal tissues.