Galectin-3 restrains spontaneous germinal centers formation preventing autoimmunity.

BECCARIA CG; FIOCCA VERNENGO F; AMEZCUA VESELY MC; RAMELLO MC; GOROSITO SERRÁN M; PIAGGIO E; MUCCI J; CAMPETELLA O; MONTES CL; ACOSTA RODRIGUEZ EV; GRUPPI A

Congreso; I Meeting LASID-FAIC-SAI.; 2015

Previously, we identified Galectin-3(Gal-3) as a critical regulator of germinal center(GC) formation and antibody production. Thus, in comparison to WT mice, Gal-3KO mice show higher: frequency of antibody-secreting-cells, serum immunoglobulin concentration, percentage of GC and T follicular helper(Tfh) cells, Tfh/T follicular regulatory ratio and IFN-γ production. Compatible with the association of spontaneous GC-formation and the development of lupus-like autoimmune diseases, we observed that aged Gal-3KO mice present autoantibodies and intense mononuclear infiltration in kidneys. Using mixed bone marrow chimeras, we sought to determine whether the spontaneous GCs development was induced by lack of Gal-3 expression specifically in the B cells. We observed that most of the GC+B cells detected in WT-Gal-3KO chimeric mice were originated from Gal-3-KO B cell progenitors. However, there were also some GC+B cells within the Gal-3-sufficient B cells, likely as result of the induction of Tfh by Gal-3+ B cells that, in turn, promote GC-differentiation from Gal-3+ B cells. Nonetheless, to confirm the intrinsic role of Gal-3 in B cells, we adoptively transferred B cells from WT and Gal-3KO mice into B-cell deficient μMT mice. We found high serum immunoglobulins levels only in mice transferred with Gal-3-deficient B cells. Phenotypic and transcriptional profiling of B cells from WT and Gal-3KO mice showed increased expression of genes related to GC-formation and costimulatory molecules involved in GC-reaction in Gal-3KO mice.These findings demonstrate that absence of Gal-3 in B cells intrinsically favors GC formation and highlight the potential for therapeutic targeting of this pathway in autoimmunity.