| First Author | Kolan SS | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 7 | Pages | e0134113 |
| PubMed ID | 26222253 | Mgi Jnum | J:301940 |
| Mgi Id | MGI:6255716 | Doi | 10.1371/journal.pone.0134113 |
| Citation | Kolan SS, et al. (2015) Non-Hematopoietic and Hematopoietic SIRPalpha Signaling Differently Regulates Murine B Cell Maturation in Bone Marrow and Spleen. PLoS One 10(7):e0134113 |
| abstractText | B lymphocyte development occurs in the bone marrow, while final differentiation and maturation can occur in both the bone marrow and the spleen. Here we provide evidence that signal regulatory protein alpha (SIRPalpha), an Ig-superfamily ITIM-receptor expressed by myeloid but not by lymphoid cells, is involved in regulating B cell maturation. Lack of SIRPalpha signaling in adult SIRPalpha-mutant mice resulted in a reduced maturation of B cells in the bone marrow, evident by reduced numbers of semi-mature IgD+IgMhi follicular type-II (F-II) and mature IgD+IgMlo follicular type-I (F-I) B cells, as well as reduced blood B cell numbers. In addition, lack of SIRPalpha signaling also impaired follicular B cell maturation in the spleen. Maturing BM or splenic B cells of SIRPalpha-mutant mice were found to express higher levels of the pro-apoptotic protein BIM and apoptosis was increased among these B cells. Bone marrow reconstitution experiments revealed that the B cell maturation defect in bone marrow and blood was due to lack of SIRPalpha signaling in non-hematopoietic cells, while hematopoietic SIRPalpha signaling was important for follicular B cell maturation in the spleen. Adding on to our previous findings of a stromal cell defect in SIRPalpha-mutant mice was the finding that gene expression of receptor activator of nuclear factor-kB ligand (RANKL) was significantly lower in cultured bone marrow stromal cells of SIRPalpha mutant mice. These data suggest a novel and opposite contribution of SIRPalpha signaling within non-hematopoietic and hematopoietic cells, respectively, to maintain B cell maturation and to prevent apoptosis in the bone marrow and spleen of adult mice. |
