The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here, we show that Casp6 regulates early B-cell development. One-week-old Casp6 knockout (Casp6 KO) mice have significantly more splenic B-cell subsets than wild-type (WT) mice. Adult Casp6 KO mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and CD43+ "transitional" or splenic red pulp (RP) B cells. These results suggested that Casp6 may function to control B-cell numbers under nonhomeostatic conditions and during B-cell development. Consistent with this model, reconstitution of B cells was dysregulated in Casp6 KO mice after sublethal irradiation. Furthermore, bone marrow pro-B, pre-B and immature B-cell numbers were significantly higher in 1-week-old Casp6 KO mice than in 1-week-old WT mice. Casp6 KO pro-B cells proliferated more in response to IL-7 than WT pro-B cells, suggesting that Casp6 regulates early B-cell responses to IL-7. Indeed, adult and aged Casp6 KO mice had elevated numbers of IL-7αR+ Sca1+ precursors of common lymphoid progenitors, suggesting Casp6 may help regulate progenitors of B cells and early B-lineage cells. Casp6 regulates B-cell programs both during early development and after antigen stimulation in the periphery.

中文翻译：

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半胱天冬酶对B谱系细胞的调节6。

蛋白酶的胱天蛋白酶（Casp）家族调节淋巴细胞凋亡和激活。在这里，我们显示Casp6调节早期B细胞发育。一周大的Casp6基因敲除（Casp6 KO）小鼠比野生型（WT）小鼠脾脏B细胞亚群明显多。成年Casp6 KO小鼠的脾脏B细胞总数正常，但B1a B细胞和CD43 +“过渡性”或脾脏红浆（RP）B细胞数量增加。这些结果表明，Casp6在非稳态条件下和B细胞发育过程中可能起着控制B细胞数量的作用。与该模型一致，在亚致死剂量照射后，Casp6 KO小鼠的B细胞重构失调。此外，在1周龄的Casp6 KO小鼠中，骨髓pro-B，pre-B和未成熟B细胞的数量明显高于1周龄的WT小鼠。Casp6 KO pro-B细胞对IL-7的反应比WT pro-B细胞增殖更多，这表明Casp6调节早期B细胞对IL-7的反应。的确，成年和成年Casp6 KO小鼠的常见淋巴祖细胞的IL-7αR+ Sca1 +前体数量增加，这表明Casp6可能有助于调节B细胞和早期B系细胞的祖细胞。Casp6在早期发育期间和外周抗原刺激后均调节B细胞程序。