Aims: Interleukin-10 (IL-10) is a pleiotropic cytokine with immunosuppressive properties that has been shown to support B cell survival. Recent studies have identified a subset of regulatory B cells that can suppress the progression of autoimmunity by production of IL-10. Previous work from our laboratory has shown that the introgression of a chromosome 4 interval spanning 32 to 150Mb from autoimmune prone New Zealand Black mice expands two innate-like lymphocyte populations, CD5⁺ B cells and Natural Killer T cells. Additional work on these mice identified the expanded splenic and peritoneal CD5⁺ B cell population as highly IL-10 competent and regulatory in nature. The aim of this study was to identify a possible role of IL-10 in the development or homeostatic expansion of NKT and CD5⁺ B cells.  

Methods: IL-10 knockout mice, obtained from Jackson laboratories, were bred onto our chromosome 4 congenic background. Congenic knockout mice and controls were aged to 18 - 23 weeks.  Splenic and peritoneal cell populations were identified de novo by flow cytometry.

Results: Similar to previous studies, the IL-10 knockout reduced the proportion of splenic Natural Killer cells on both the B6 and chromosome 4 backgrounds when compared to IL-10 sufficient controls. Interestingly, IL-10 knockout had no impact on the expansion of splenic NKT cells, suggesting that IL-10 is not important in the expansion of this population. Surprisingly, IL-10 knockout prevented the expansion of both splenic and peritoneal CD5⁺ B cells in chromosome 4 congenic mice and greatly expanded the splenic marginal zone compartment.

Conclusions: Taken together, these data indicate that IL-10 may play a unique and critical role in sustaining the genetic expansion of CD5⁺ B cells in the splenic and peritoneal compartments. Unlike previous reports, this study suggests that the expansion of regulatory B cells may be impacted by the loss of IL-10.