Galectin-3 restrains spontaneous germinal centers formation preventing autoimmunity

BECCARÍA C; FIOCCA F; AMEZCUA VESELY C; TOSELLO BOARI J; GOROSITO M; PIAGGIO E; MUCCI J; CAMPETELLA O; MONTES CL; ACOSTA RODRIGUEZ EV; GRUPPI A

Buenos Aires

Congreso; I meeting LASID, FAIC and SAI; 2015

LASID, FAIC y SAI

Abstract: Previously, we identified Galectin-3(Gal-3) as a criticalregulator of germinal center(GC) formation and antibodyproduction. Thus, in comparison to WT mice, Gal-3KO miceshow higher: frequency of antibody-secreting-cells, serumimmunoglobulin concentration, percentage of GC and T follicularhelper(Tfh) cells, Tfh/T follicular regulatory ratio and IFN-􀈖production. Compatible with the association of spontaneous GCformationand the development of lupus-like autoimmunediseases, we observed that aged Gal-3KO mice presentautoantibodies and intense mononuclear infiltration in kidneys.Using mixed bone marrow chimeras, we sought to determinewhether the spontaneous GCs development was induced by lackof Gal-3 expression specifically in the B cells. We observed thatmost of the GC+B cells detected in WT-Gal-3KO chimeric micewere originated from Gal-3-KO B cell progenitors. However,there were also some GC+B cells within the Gal-3-sufficient Bcells, likely as result of the induction of Tfh by Gal-3+ B cellsthat, in turn, promote GC-differentiation from Gal-3+ B cells.Nonetheless, to confirm the intrinsic role of Gal-3 in B cells, weadoptively transferred B cells from WT and Gal-3KO mice into Bcelldeficient μMT mice. We found high serum immunoglobulinslevels only in mice transferred with Gal-3-deficient B cells.Phenotypic and transcriptional profiling of B cells from WT andGal-3KO mice showed increased expression of genes related toGC-formation and costimulatory molecules involved in GCreactionin Gal-3KO mice.These findings demonstrate that absence of Gal-3 in B cellsintrinsically favors GC formation and highlight the potential fortherapeutic targeting of this pathway in autoimmunity.