B cell glycosylation modulates mucosal immunity in experimental models of colitis

MOROSI, LUCIANO; MARTINEZ ALLO, VERONICA; MAY, MARÍA; MARIÑO, KARINA V.; CUTINE, ANABELA M.; CAGNONI, ALEJANDRO J.; GATTO, SABRINA; TOSCANO, MARTA A; MANSELLE COCCO, MONTANA; MORALES, ROSA; RABINOVICH, GABRIEL A.

San Martín, Buenos Aires

Simposio; Tercer Simposio Argentino de Glicobiología GlycoAr 2019; 2019

IBYME/ Fun Leloir/ Universidad de San Martín/ CIBICIQ

The glycome of immune cells is a key regulator of cellular processes relevant to health and disease. It has been shown that development of intestinal inflammation alters T cell glycosylation, 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 and plasma cells, negatively affecting their tolerogenic role duringcolitis. Our results show that the 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-/-), a glycosyltransferase 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 of α2,6sia specifically on B cells, we cotransferred into RAG2-/- mice colitogenic-CD4+CD45RBhi T cellswith B cells isolated from either WT or ST6Gal1-/- mice. While cotransfer with WT B cells reduced colonic T cell infiltration, cotransferring with ST6Gal1-/- B cells resulted in higher inflammation, and lower amounts of both fecal IgA and PCs when compared to WT B cells. Collectively, our results suggest that α2,6sia exerts a regulatory role on B cells during IBD and provide a potential mechanism for the modulation of B cell functionality on inflamed intestinal tissues.