on T and B Lymphocyte Development2 Gene Deletion a 1 and T3R a Effects of T3R

3 Thyroid hormones bind to several nuclear receptors encoded by T3R a and T3R b genes. There is now accumulating evidence that thyroid hormones act on the immune system. Indeed, mice deficient for thyroid hormones show a reduction in lymphocyte production. However, the mechanisms involved and, in particular, the role of the different thyroid hormone receptors in lymphocyte development have not been investigated. To address that question, we have studied lymphocyte development in mice deficient for the T3R a 1 and T3R a 2 gene products. A strong decrease in spleen cell numbers was found compared with wild-type littermates, B lymphocytes being more severely affected than T lymphocytes. A significant decrease in splenic macrophage and granulocyte numbers was also found. In bone marrow, a reduction in CD45 1 /IgM 2 pro/pre-B cell numbers was found in these mice compared with wild-type littermates. This decrease seems to result from a proliferation defect, as CD45 1 /IgM 2 cells incor-porate less 5-bromo-2 * -deoxyuridine in vivo. To define the origin of the bone marrow development defect, chimeric animals between T3R a 2 / 2 and Rag1 2 / 2 mice were generated. Results indicate that for B cells the control of the population size by T3R a 1 and T3R a 2 is intrinsic. Altogether, these results show that T3R a 1 or T3R a 2 gene products are implicated in the control of the B cell pool size. The Journal of Immunology, 2000, 164: 152–160. KO mice and wild-type littermates were injected twice i.p. at a 30-min interval with 1 mg BrdU. This thymidine analogue is in-corporated in the DNA of cycling cells. Incorporation of BrdU in bone marrow and thymic cells was measured 6 h after the last injec-tion. Cells were first stained for surface markers to identify lymphocyte subsets. BrdU 1 cells were then revealed by a FITC-conjugated anti-BrdU Ab, as described in Materials and Methods . PBS-injected animals were used as a negative control for background staining.