Alpha-(2,6) Sialylation influences B Cell functionality in the mucosal compartment

MOROSI L; GATTO S; MAY M; TOSCANO MA; CUTINE AM; MORALES R; MAHMOUD Y; MARTÍNEZ ALLO V; RABINOVICH GA; SASSO FERRER M; GIROTTI MR; MARIÑO KV

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Glycosylation is a common post-translational modification that has the potential to regulate cellular processes relevant to immune tolerance and disease. Here, we aim to examine the impact of α(2,6) sialylation (α2,6sia) on B-cell functionality, specifically in the context of intestinal immunity. Working with α(2,6) sialyltransferase (ST6Gal1) deficient mice, we found that these animals exhibit decreased percentage of IgA+ plasma cells (PCs) in the intestinal lamina propria and alterations in fecal bacterial coating with IgA; 16S rRNA gene sequencing analysis of fecal microbiota also showed significant differences in bacterial composition and a reduction in diversity compared to WT mice. In order to study α(2,6)sia influence on B-cells during intestinal inflammation, we established a chronic T-cell transfer model of colitis in RAG2-/- mice. Co-transfer of CD4+CD45RBhi T-cells and WT B-cells reduced colonic inflammation and IFN-γ expression in lamina propria (LP). However, co-transference with ST6Gal1-/- B-cells resulted in decreased percentage of B-cells in mesenteric lymph nodes, lower amounts of IgA+ plasma cells and increased number of CD4+ T-cells in LP. Additionally, we observed a decreased percentage of IgA-coated bacteria when compared to co-transference of WT B-cells. These results show an unrecognized role of sialic acid in the mucosal compartment, B-cell functionality and reveal potentially novel mechanistic roles for B-cell glycobiology in intestinal inflammation.