B cell glycosylation modulates mucosal immunity in experimental models of colitis

CUTINE, ANABELA; LUCIANO MOROSI; MANSELLE COCCO, MONTANA; CAGNONI, ALEJANDRO J.; MARTINEZ ALLO, VERÓNICA; MORALES, ROSA; GATTO, SABRINA; RABINOVICH, GABRIEL A.; TOSCANO, MARTA; RABINOVICH, GABRIEL A.

San Martín, Buenos Aires

Congreso; GlycoAr 2019; 2019

Sociedad Argentina de Glicobiología

The glycome of immune cells is a key regulator of cellularprocesses relevant to health and disease. It has been shown thatdevelopment of intestinal inflammation alters T cell glycosylation,contributing to the exacerbation of inflammatory bowel diseases(IBD). However, the glycome of other immune cells during colitisremains poorly described. Here, we demonstrate that chronicinflammation alters glycosylation in both B lymphocytes andplasma cells, negatively affecting their tolerogenic role duringcolitis. Our results show that the glycome of colonic B cells andIgA+ plasma cells (PCs) from mice coursing DSS-induced chroniccolitis presented lower levels of surface α2,6-sialylation (α2,6sia).Thus, we examined the lack of α2,6sia in either WT or ST6Gal1deficient animals (ST6Gal1-/-), a glycosyltransferase that addsα2,6sia to N-glycans. ST6Gal1-/- mice develop more severedisease signs and inflammatory score as a result of DSS colitis.To investigate the role of α2,6sia specifically on B cells, we cotransferredinto RAG2-/- mice colitogenic-CD4+CD45RBhi T cellswith B cells isolated from either WT or ST6Gal1-/- mice. While cotransferwith WT B cells reduced colonic T cell infiltration, cotransferringwith ST6Gal1-/- B cells resulted in higherinflammation, and lower amounts of both fecal IgA and PCs whencompared to WT B cells. Collectively, our results suggest thatα2,6sia exerts a regulatory role on B cells during IBD and providea potential mechanism for the modulation of B cell functionalityon inflamed intestinal tissues.