CD38 Deficiency Ameliorates Chronic Graft--Host Disease Murine Lupus a B-Cell-Dependent Mechanism.

The absence of the mouse cell surface receptor CD38 in 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--host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic 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-betCD11c B cells, were observed in mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of B cells to respond to allogeneic help from bm12 CD4 T cells is greatly diminished. The frequencies of T-betCD11c 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 cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses.