ALPHA-(2,6) SIALYLATION INFLUENCES B CELL FUNCTIONALITY IN THE MUCOSAL COMPARTMENT

MARTA A. TOSCANO; MARÍA MAY; SABRINA GATTO; LUCIANO G. MOROSI; MARTA A. TOSCANO; MARÍA MAY; SABRINA GATTO; LUCIANO G. MOROSI; GABRIEL A. RABINOVICH; YAMIL MAHMOUD; ROSA MORALES; KARINA V. MARIÑO; ANABELA M. CUTINE; MARÍA ROMINA GIROTTI; GABRIEL A. RABINOVICH; MARIANELA SASSO FERRER; YAMIL MAHMOUD; VERÓNICA MARTINEZ ALLO; ROSA MORALES; KARINA V. MARIÑO; ANABELA M. CUTINE; MARÍA ROMINA GIROTTI; MARIANELA SASSO FERRER; VERÓNICA MARTINEZ ALLO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC, SAI

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. In a α(2,6) sialyltransferase (ST6Gal1) KO mouse model, we found that the animals exhibited a decreased percentage of IgA+ plasma cells (PCs) in the intestinal lamina propria and alterations in fecal bacterial coating with IgA. Moreover, 16S rRNA gene sequencing analysis of fecal microbiota also showed significant differences in bacterial composition and a reduction in diversity compared to wild type (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.