Non-Hematopoietic and Hematopoietic SIRP? Signaling Differently Regulates Murine B Cell Maturation in Bone Marrow and Spleen.

ABSTRACT: 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 ? (SIRP?), an Ig-superfamily ITIM-receptor expressed by myeloid but not by lymphoid cells, is involved in regulating B cell maturation. Lack of SIRP? signaling in adult SIRP?-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 SIRP? signaling also impaired follicular B cell maturation in the spleen. Maturing BM or splenic B cells of SIRP?-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 SIRP? signaling in non-hematopoietic cells, while hematopoietic SIRP? signaling was important for follicular B cell maturation in the spleen. Adding on to our previous findings of a stromal cell defect in SIRP?-mutant mice was the finding that gene expression of receptor activator of nuclear factor-?B ligand (RANKL) was significantly lower in cultured bone marrow stromal cells of SIRP? mutant mice. These data suggest a novel and opposite contribution of SIRP? 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.

SUBMITTER: Kolan SS 

PROVIDER: S-EPMC4519279 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature