Activated B cell transcriptome induced by mATG treatment of heart allograft recipients

Le résumé fourni par la source

Abstract After transplant recipient treatment with anti-thymocyte globulin (ATG), B cells recover and drive reconstitution of depletion-resistant memory T cells. This study investigated the effects of ATG depletion on B cells in transplant recipients. Experimental groups were: 1) BALB/c to B6 heart Tx; 2) heart Tx + ATG; 3) ATG alone; 4) naïve B6. Spleen cells were isolated on d. 8 posttransplant and analyzed by single cell RNA-seq. Across all B cell subsets, immune stimulatory genes including lymphotoxin A and B, MHC-related and costimulatory genes were increased in Heart Tx + ATG group. Despite T cell depletion, recipients of heart Tx + ATG had twice as many germinal center (GC) B cells with increased expression of MHC II-associated and costimulatory genes as other groups and uniquely showed signs of early IgG class switching in GC and plasma cells. Heart Tx + ATG treatment induced a robust interferon response signature across B cell subsets, quite strikingly in the marginal zone (MZ) and transitional B cells. Targeting MZ B cells with anti-integrin mAb or the use MZ B cell-deficient recipients delayed recovery of CD8 T lymphocytes compared to controls suggesting that interferon signaling in MZ B cells is driving their proinflammatory functions required for T cell reconstitution. In sum, ATG lymphoablation induce proinflammatory signature in recipient B cells consistent with their role in T cell homeostatic expansion and raising a possibility of enhanced humoral responses.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.