The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus

Previous work from our group has shown that Cd38-/- mice develop a milder pristane-induced lupus disease than WT or Art2-/- counterparts, demonstrating a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via a Transient Receptor Potential Melastatin 2 (TRPM2)-dependent apoptosis-driven mechanism. In this study we asked whether CD38 may play a role in the expression and function of regulatory B cells (IL-10-producing B cells or B10 cells). In pristane-treated mice the frequency of spleen CD19+CD1dhiCD5+ B cells, which are highly enriched in B10 cells, was significantly increased in Cd38-/- splenocytes compared to WT, while the frequency of peritoneal plasmacytoid dendritic cells (pDCs), which are major type I Interferon (IFN) producers, was greatly diminished. The low proportion of pDCs correlated with lower amounts of IFN-α in the peritoneal lavage fluids of the Cd38-/- mice than of WT and Art2-/- mice. Functional ex vivo assays showed increased frequencies of IL-10-producing B cells in Cd38-/- splenocytes than in WT upon stimulation with an agonist anti-CD40 mAb. Overall these results strongly suggest that Cd38-/- mice are better suited than WT mice to generate and expand regulatory B10 cells following the appropriate stimulation.Work performed in the Sancho and Zubiaur labs was supported in part by the European Commission in collaboration with the following Funding Agencies: (i) Junta de Andalucía, Consejería Innovación Ciencia y Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to Jaime Sancho and Mercedes Zubiaur, and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 and SAF-2017-89801-R to Jaime Sancho and Mercedes Zubiaur. The stay of B.B. and G.R. in Sancho’s lab was supported by National Science Foundation: Grant #HRD-0963629 (G-STEM). USA.; and U.S. Department of Education; Student Aid and Fiscal Responsibility Act; Title III Grant (SAFRA, Part F). Grant SAF-2017-89801-R covers in part the costs to publish in open access