B cell activation contributes to splenomegaly in PPARγ deficient mice (153.21)

Abstract

Abstract PPARγ is a nuclear transcription factor that modulates diverse biofunctions, including lipid biosynthesis, glucose metabolism and inflammation. However, the specific role of PPARγ in the immune function has not been fully explored. We have previously generated mice with PPARγ gene expression from 25% to 100% normal. We found that mice with 25% expression of PPARγ (PpargC/-) exhibited a two-fold increase in spleen size at their young age and lasted throughout the life. It has been demonstrated PPARγ deficiency enhanced bone formation and relocated hematopoiesis to the spleen. However, micro-CT analysis showed trabecular volume, number, thickness, and bone mineral density were increased in old, but not in young, PpargC/- mice. The population of hematopoietic stem cells (HSCs) and the expression level of transcription factors, crucial for HSC differentiation and self-renewal, in spleen were also increased in old PpargC/- mice. However, young PpargC/- with splenomegaly revealed neither increased bone formation nor relocation of hematopoiesis to the spleen. In vivo BrdU incorporation study demonstrated that B cells were highly proliferated in young PpargC/- mice. Therefore, further studies are needed to examine the role of PPARγ in immune system. These results suggest that splenomegaly in young PpargC/- mice was not likely caused by extramedullary hematopoiesis, but may be contributed by increased activation of B cells, implicating the beneficial role of PPARγ in immunomodulation.