First Author | Watanabe C | Year | 2018 |
Journal | Immunol Cell Biol | Volume | 96 |
Issue | 10 | Pages | 1072-1082 |
PubMed ID | 29863787 | Mgi Jnum | J:319823 |
Mgi Id | MGI:6730550 | Doi | 10.1111/imcb.12172 |
Citation | Watanabe C, et al. (2018) Regulation of B-lineage cells by caspase 6. Immunol Cell Biol 96(10):1072-1082 |
abstractText | 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-7alphaR(+) 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. |