Peroxisome proliferator-activated receptor α regulates B lymphocyte development via an indirect pathway in mice

Peroxisome proliferator-activator receptor et (PPARalpha), a member of the nuclear receptor superfamily, has been implicated in the regulation of inflammation and immune response. Adaptive immune responses are suppressed by exposure to PPARalpha agonists, resulting in severe thymus and spleen atrophy. In addition, the decline in both T and B cells is due in part to the loss of splenocytes upon exposure to PPARalpha agonists. Thus, the current study was designed to examine the effect of Wy-14,643, a potent PPARalpha agonist, on B cell development in bone marrow from wild-type and PPARalpha-null mice. Significantly decrease in pro/pre-B cell and total B220(+) cell was observed in wild-type mice in bone marrow upon Wy-14,643 treatment, but not in PPARalpha-null mice. Immature and mature B cell populations are not affected. This suggests that PPARalpha is involved in the development of B cell during lymphoid lineage. However, surprisingly, PPARalpha mRNA was absent in bone marrow as revealed by RT-PCR. Therefore, the effect of PPARalpha on B cell development is by an indirect mechanism. (C) 2004 Elsevier Inc. All rights reserved.