Dissecting the role of Galectin-3, IFN-γ and microbiota in Germinal Center B cell fate decisions.

GRUPPI, ADRIANA; CAMPETELLA, OSCAR; MUCCI, JUAN; FIOCCA VERNENGO, FACUNDO; MONTES, CAROLINA L; RAMELLO, MARIA CECILIA; AMEZCUA VESELY, MARIA CAROLINA; ACOSTA RODRIGUEZ E V; TOSELLO BOARI, JIMENA; ALMADA, LAURA; BECCARIA, CRISTIAN GABRIEL

Buenos Aires

Congreso; Reunion conjunta de sociedades de Biociencias; 2017

SAI - SAIC - SAP - SAIB etc

(1289) DISSECTING THE ROLE OF GALECTIN-3, IFN-γAND MICROBIOTA IN GERMINAL CENTER B CELL FATEDECISIONS.Cristian Gabriel Beccaria (1), Facundo Fiocca Vernengo (1),María Carolina Amezcua Vesely (1), Laura Almada (1), JuanMucci (2), María Cecilia Ramello (1), Jimena Tosello Boari(1), Oscar Campetella (2), Carolina Lucia Montes (1), EvaVirginia Acosta Rodriguez (1), Adriana Gruppi (1)(1) Centro de Investigaciones en Bioquímica Clínica e Inmunología(CIBICI)-CONICET, Facultad de Ciencias Químicas,Universidad Nacional de Córdoba, X5000HUA, Córdoba,Argentina. (2) Instituto de Investigaciones Biotecnológicas,Universidad Nacional de San Martín, San Martín, Argentina.Germinal Centers (GC) are unique structures where high affinityantibodies and memory B cells are generated. With the aim of ensurefast selection of rapidly evolving clones in GCs, follicular dendriticcells, GC B cells and T cells engage in multiple interactions.So far, only co-stimulatory or inhibitory membrane immune receptor/ligand pairs and cytokines have been investigated and are knownto be involved in this process. However, there is a pressing need tounderstand other factors that regulate GCs in order to optimize andcontrol humoral responses following vaccination, antibody-mediatedautoimmune diseases, and GC B cell-derived malignancies. Here,we report a novel effector function by which Galectin-3 (Gal-3), aβ-galactoside binding protein, is critically involved in the developmentof GCs. Gal-3 KO mice exhibit high frequency of spontaneousGC (sGC) B cells and T follicular helper (Tfh) cells that correlatedwith hypergammaglobulinemia, high amounts of IFN-γ in serumand lupus-like autoimmune manifestations. We found that the mainsource of IFN-γ in Gal-3 KO mice were CD4+ T cells (including Tfh),since there are no significant differences between IFN-γ-producingCD8 T, NK, NKT and DCs cells between groups. IFN-γ blockade inGal-3 KO mice prevents the autoimmune condition, demonstratingthat IFN-γ overproduction sustain lupus-like disease. We were alsowondering whether specific microbiota in Gal-3 mice could influencethe induction of sGCs. Microbiota modulation by antibiotic treatmentcould not prevent sGCs induction in Gal-3 KO mice and, interestingly,these mice did not modify the generation of GCs in Peyer?spatches after treatment, unlike the WT mice which showed a deepreduction of them. Finally, using chimeric mice with B cell-specificdeficiency of Gal-3, we reveal that intrinsic Gal-3 signaling in B cellscontrol sGC formation. Together, our data provide the first evidencethat Gal-3 acts directly on B cells regulating GCs responses viaIFN-γ.Keywords: Germinal Centers; Galectin-3; Autoimmunity; IFN-γ; Bcell Immunology.