First Author | Burlock B | Year | 2018 |
Journal | Int J Mol Sci | Volume | 19 |
Issue | 10 | PubMed ID | 30257456 |
Mgi Jnum | J:295650 | Mgi Id | MGI:6454173 |
Doi | 10.3390/ijms19102906 | Citation | Burlock B, et al. (2018) The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus. Int J Mol Sci 19(10):2906 |
abstractText | 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(+)CD1d(hi)CD5(+) 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-alpha 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. |