AUTHOR=Martínez-Blanco África , Domínguez-Pantoja Marilú , Botía-Sánchez María , Pérez-Cabrera Sonia , Bello-Iglesias Nerea , Carrillo-Rodríguez Paula , Martin-Morales Natividad , Lario-Simón Antonio , Pérez-Sánchez-Cañete María M. , Montosa-Hidalgo Laura , Guerrero-Fernández Salvador , Longobardo-Polanco Victoria M. , Redondo-Sánchez Sandra , Cornet-Gomez Alberto , Torres-Sáez María , Fernández-Ibáñez Ana , Terrón-Camero Laura , Andrés-León Eduardo , O’Valle Francisco , Merino Ramón , Zubiaur Mercedes , Sancho Jaime 

TITLE=CD38 Deficiency Ameliorates Chronic Graft-Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.713697

DOI=10.3389/fimmu.2021.713697

ISSN=1664-3224

ABSTRACT=Absence of mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as positive regulator of inflammatory and autoimmune responses. Here we report that in the setting of a chronic graft versus host disease (cGVHD) lupus model induced by the transfer of B6.C-H2bm12/KhEg (bm12) spleen cells into co-isogenic Cd38-/- B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells and T-bet+CD11chi B cells are observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells, and Tfr cells is normal, suggesting that the ability of Cd38-/- B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody secreting cells, correlate with anti-ssDNA autoantibody serum levels, with IL-27, and sCD40L. Proteomics profiling of spleens from WT cGVHD mice reflects a STAT1-driven type I IFN-signature, which is absent in Cd38-/- cGVHD mice. Kidney, spleen and liver inflammation was mild and resolved faster in Cd38-/- cGVHD mice than in WT cGVHD mice. We conclude that in B cells CD38 functions as a modulator receptor that controls autoimmune responses. "Proteomic Data are available via ProteomeXchange with identifier PXD026947."