Regulation of B‐lineage cells by caspase 6

• Published in: Immunology and cell biology 2018-11, Vol.96 (10), p.1072-1082
• Main Authors: Watanabe, Chie, Shu, Geraldine L, Giltiay, Natalia V, Clark, Edward A
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis; Ataxin; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bone marrow; Caspase; Caspase 6 - genetics; Caspase 6 - metabolism; Caspase-6; CD43 antigen; Cell activation; Cells; Evolution & development; Immunomodulation; Interleukin 7; Interleukin-7 - metabolism; Lymphocytes B; Lymphoid Progenitor Cells - cytology; Lymphoid Progenitor Cells - metabolism; Lymphopoiesis; Male; Mice; Mice, Knockout; Peyer's Patches - immunology; Peyer's Patches - metabolism; Proteases; Radiation; Red pulp; Rodents; Spleen; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Stem cells
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1111/imcb.12172

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. The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here, we show that Casp6 regulates early B‐cell development. Our data suggest Casp6 may help regulate progenitors of B cells and early B‐lineage cells.