Wang, NinghaiYigit, Burcuvan der Poel, Cees E.Cuenca, MartaCarroll, Michael C.Herzog, Roland W.Engel, PabloTerhorst, Cox2019-08-202019-08-202019-04-17Wang, N., Yigit, B., van der Poel, C. E., Cuenca, M., Carroll, M. C., Herzog, R. W., … Terhorst, C. (2019). The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease. Frontiers in immunology, 10, 831. doi:10.3389/fimmu.2019.00831https://hdl.handle.net/1805/20450Absence of the mouse cell surface receptor SLAMF3 in SLAMF3-/- mice suggested that this receptor negatively regulates B cell homeostasis by modulating activation thresholds of B cell subsets. Here, we examine whether anti-SLAMF3 affects both B and T cell subsets during immune responses to haptenated ovalbumin [NP-OVA] and in the setting of chronic graft vs. host disease (cGVHD) induced by transferring B6.C-H2 bm12/KhEg (bm12) CD4+ T cells into B6 WT mice. We find that administering αSLAMF3 to NP-OVA immunized B6 mice primarily impairs antibody responses and Germinal center B cell [GC B] numbers, whilst CXCR5+, PD-1+, and ICOS+ T follicular helper (TFH) cells are not significantly affected. By contrast, administering αSLAMF3 markedly enhanced autoantibody production upon induction of cGVHD by the transfer of bm12 CD4+ T cells into B6 recipients. Surprisingly, αSLAMF3 accelerated both the differentiation of GC B and donor-derived TFH cells initiated by cGVHD. The latter appeared to be induced by decreased numbers of donor-derived Treg and T follicular regulatory (TFR) cells. Collectively, these data show that control of anti-SLAMF3-induced signaling is requisite to prevent autoantibody responses during cGVHD, but reduces responses to foreign antigens.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesB cellsSLAMF3AlloimmunityAutoreactivecGVHDArticle