Smithson G, Couse J F, Lubahn D B, Korach K S, Kincade P W
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
J Immunol. 1998 Jul 1;161(1):27-34.
Several observations suggest that sex steroids might participate in steady state regulation of B lymphopoiesis. B cell precursors decline dramatically in bone marrow of pregnant or estrogen-treated mice. Reciprocally, the same cell populations are increased in hypogonadal mice or male castrates. Estrogen treatment of hypogonadal mice reduced precursors to normal. However, questions remain about which hormones and receptors are the most important. Furthermore, these observations need to be reconciled with advances regarding new sex steroid receptors. We have now characterized B lymphopoiesis in androgen receptor-deficient testicular feminization (Tfm) mice. Testicular feminization mice had substantially elevated numbers of B cell precursors in the bone marrow and B cells in the spleen as compared with wild-type mice. The importance of one estrogen receptor (ER alpha) was evaluated in gene-targeted mice, and B cell precursors were found to be within the normal range. Our previous studies indicated that hormone receptors in stromal cells may be important for estrogen-mediated suppression of B lymphopoiesis. We now show that estrogen-mediated inhibition of B cell precursor expansion in culture was blocked by a specific estrogen receptor antagonist (ICI 182,780). Stromal cells derived from ER alpha-targeted bone marrow were fully estrogen responsive. RT-PCR analyses of these stromal cells revealed splice-variant transcripts of ER alpha, as well as message for a recently discovered estrogen-binding receptor, ER beta. Thus, androgens may normally inhibit B lymphopoiesis through the androgen receptor, whereas estrogens might utilize one or more receptors to achieve the same physiologic response.
多项观察结果表明，性类固醇可能参与B淋巴细胞生成的稳态调节。在怀孕小鼠或接受雌激素处理的小鼠骨髓中，B细胞前体显著减少。相反，在性腺功能减退的小鼠或雄性去势小鼠中，相同的细胞群体数量增加。对性腺功能减退的小鼠进行雌激素处理可使前体恢复正常。然而，关于哪些激素和受体最为重要的问题依然存在。此外，这些观察结果需要与新的性类固醇受体方面的进展相协调。我们现在已经对雄激素受体缺陷的睾丸雌性化（Tfm）小鼠的B淋巴细胞生成进行了特征描述。与野生型小鼠相比，睾丸雌性化小鼠骨髓中的B细胞前体数量以及脾脏中的B细胞数量大幅增加。在基因靶向小鼠中评估了一种雌激素受体（ERα）的重要性，发现B细胞前体数量在正常范围内。我们之前的研究表明，基质细胞中的激素受体可能对雌激素介导的B淋巴细胞生成抑制作用很重要。我们现在表明，培养中雌激素介导的B细胞前体扩增抑制作用被一种特异性雌激素受体拮抗剂（ICI 182,780）阻断。源自ERα靶向骨髓的基质细胞对雌激素完全有反应。对这些基质细胞进行的RT-PCR分析揭示了ERα的剪接变体转录本，以及一种最近发现的雌激素结合受体ERβ的信息。因此，雄激素可能通常通过雄激素受体抑制B淋巴细胞生成，而雌激素可能利用一种或多种受体来实现相同的生理反应。
