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Front Immunol ; 12: 713697, 2021.
Article in English | MEDLINE | ID: mdl-34504495

ABSTRACT

The absence of the mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, 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, were observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells and Tfr cells was 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, IL-27, and sCD40L. Proteomics profiling of the 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 CD38 in B cells functions as a modulator receptor that controls autoimmune responses.


Subject(s)
ADP-ribosyl Cyclase 1/deficiency , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Disease Susceptibility , Graft vs Host Disease/etiology , Graft vs Host Disease/metabolism , Membrane Glycoproteins/deficiency , Adoptive Transfer , Animals , Autoantibodies/blood , Autoantibodies/immunology , Autoimmunity , Biomarkers , Chronic Disease , Cytokines/metabolism , Disease Models, Animal , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/therapy , Immunophenotyping , Lupus Erythematosus, Systemic/etiology , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Lymphocyte Count , Mice , Mice, Knockout , Organ Specificity , Proteome , Proteomics/methods , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism
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