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The Journal of Immunology, 2003, 171: 1667-1675.
Copyright © 2003 by The American Association of Immunologists

Lymphocyte Accumulation in the Spleen of Retinoic Acid Receptor-Related Orphan Receptor {gamma}-Deficient Mice1

Nu Zhang, Jian Guo and You-Wen He2

Department of Immunology, Duke University Medical Center, Durham, NC 27710

The hormone nuclear receptor retinoic acid receptor-related orphan receptor {gamma} (ROR{gamma}) plays important roles in thymocyte development and lymphoid organogenesis. ROR{gamma} and its thymus-specific isoform ROR{gamma}t are expressed in the thymus, but not in the spleen and bone marrow (BM). However, ROR{gamma}-/- 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 ROR{gamma}-/- 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 ROR{gamma}-/- or recombinase-activating gene-2-/- mice as recipients and wild-type or ROR{gamma}-/- mice as donors, respectively, demonstrate that the splenic microenvironment of ROR{gamma}-/- 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 ROR{gamma}-/- mice. Collectively, these results suggest that ROR{gamma} regulates lymphocyte homeostasis at multiple levels.




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[Abstract] [Full Text] [PDF]


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