title: Non-Hematopoietic and Hematopoietic SIRPα 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 α (SIRPα), an Ig-superfamily ITIM-receptor expressed by myeloid but not by lymphoid cells, is involved in regulating B cell maturation. Lack of SIRPα signaling in adult SIRPα-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 SIRPα signaling also impaired follicular B cell maturation in the spleen. Maturing BM or splenic B cells of SIRPα-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 SIRPα signaling in non-hematopoietic cells, while hematopoietic SIRPα signaling was important for follicular B cell maturation in the spleen. Adding on to our previous findings of a stromal cell defect in SIRPα-mutant mice was the finding that gene expression of receptor activator of nuclear factor-ĸB ligand (RANKL) was significantly lower in cultured bone marrow stromal cells of SIRPα mutant mice. These data suggest a novel and opposite contribution of SIRPα 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.
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Shrikant Shantilal
authors.initials: SS
authors.lastname: Kolan
authors.affiliation: Department of Clinical Microbiology, Section for Immunology, Umeå University, Umeå, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lejon
authors.affiliation: Department of Odontology, Umeå University, Umeå, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Koskinen Holm
authors.affiliation: Department of Odontology, Umeå University, Umeå, Sweden.
authors.forename: Rima
authors.initials: R
authors.lastname: Sulniute
authors.affiliation: Department of Odontology, Umeå University, Umeå, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Molecular and Cellular Signaling, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D001853:Bone Marrow / Q000276:immunology*; D002452:Cell Count; D005260:Female; D006410:Hematopoiesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology*
chemical_list: C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic