B-cell-specific-peroxisome proliferator-activated receptor γ deficiency augments contact hypersensitivity with impaired regulatory B cells.

Nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ) activation can prevent immunoinflammatory disorders and diabetes. B cells play protective roles during inflammation as well. However, the roles of endogenous PPAR-γ in the regulatory properties of B cells to relieve inflammation remain unknown. Here, we developed B-cell-specific PPAR-γ knockout (B-PPAR-γ-/- ) mice and found that the conditional deletion of PPAR-γ in B cells resulted in exaggerated contact hypersensitivity (CHS). Meanwhile, interferon-γ (IFN-γ) of CD4+ CD8+ T cells was up-regulated in B-PPAR-γ-/- mice in CHS. This showed that the regulatory function of B cells in B-PPAR-γ-/- mice declined in vivo. Whereas splenic CD5+ CD1dhi regulatory B-cell numbers and peripheral regulatory T-cell numbers were not changed in naive B-PPAR-γ-/- mice. Loss of PPAR-γ in B cells also did not affect either CD86 or FasL expression in splenic CD5+ CD1dhi regulatory B cells after activation. Notably, interleukin-10 (IL-10) production in CD5+ CD1dhi regulatory B cells reduced in B-PPAR-γ-deficient mice. In addition, functional IL-10-producing CD5+ CD1dhi regulatory B cells decreased in B-PPAR-γ-/- mice in the CHS model. These findings were in accordance with augmented CHS. The current work indicated the involvement of endogenous PPAR-γ in the regulatory function of B cells by disturbing the expansion of IL-10-positive regulatory B cells.