Lymphocyte accumulation in the spleen of retinoic acid receptor-related orphan receptor γ-deficient mice

The hormone nuclear receptor retinoic acid receptor-related orphan receptor γ (RORγ) plays important roles in thymocyte development and lymphoid organogenesis. RORγ and its thymus-specific isoform RORγt are expressed in the thymus, but not in the spleen and bone marrow (BM). However, RORγ^-/- mice have 2- to 3-fold more splenocytes than wild-type controls due to an accumulation of conventional resting B lymphocytes. The increase in B lymphocytes in RORγ^-/- mice is caused neither by abnormal B cell development in the BM nor by an obvious defect in the peripheral T cell compartment. Furthermore, analyses of BM chimeras using either RORγ^-/- or recombinase-activating gene-2^-/- mice as recipients and wild-type or RORγ ^-/- mice as donors, respectively, demonstrate that the splenic microenvironment of RORγ^-/- mice is defective, since wild-type T and B lymphocytes accumulated in these chimeric mice. In addition, T lymphocyte homeostasis was altered due to a lowered thymic output in RORγ^-/- mice. Collectively, these results suggest that RORγ regulates lymphocyte homeostasis at multiple levels.