B-Cell-Specific-Peroxisome Proliferator-Activated Receptor Gamma Deficiency Augments Contact Hypersensitivity With Impaired Regulatory B Cells

Nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) activation can prevent immunoinflammatory disorders and diabetes. B cells play protective roles during inflammation as well. However, the roles of endogenous PPAR-gamma in the regulatory properties of B cells to relieve inflammation remain unknown. Here, we developed B-cell-specific PPAR-gamma knockout (B-PPAR-gamma(-/-)) mice and found that the conditional deletion of PPAR-gamma in B cells resulted in exaggerated contact hypersensitivity (CHS). Meanwhile, interferon-gamma (IFN-gamma) of CD4(+) CD8(+) T cells was up-regulated in B-PPAR-gamma(-/-) mice in CHS. This showed that the regulatory function of B cells in B-PPAR-gamma(-/-) mice declined in vivo. Whereas splenic CD5(+) CD1d(hi) regulatory B-cell numbers and peripheral regulatory T-cell numbers were not changed in naive B-PPAR-gamma(-/-) mice. Loss of PPAR-gamma in B cells also did not affect either CD86 or FasL expression in splenic CD5(+) CD1d(hi) regulatory B cells after activation. Notably, interleukin-10 (IL-10) production in CD5(+) CD1d(hi) regulatory B cells reduced in B-PPAR-gamma-deficient mice. In addition, functional IL-10-producing CD5(+) CD1d(hi) regulatory B cells decreased in B-PPAR-gamma(-/-) mice in the CHS model. These findings were in accordance with augmented CHS. The current work indicated the involvement of endogenous PPAR-gamma in the regulatory function of B cells by disturbing the expansion of IL-10-positive regulatory B cells.