title: Lack of non-hematopoietic SIRPα signaling disturbs the splenic marginal zone architecture resulting in accumulation and displacement of marginal zone B cells.
abstract: Signal regulatory protein α (SIRPα) is an immunoglobulin super family protein predominantly expressed by myeloid but not lymphoid cells, and its role in lymphocyte homeostasis and function is still to be revealed. We demonstrate that mice bearing a mutant SIRPα lacking the cytoplasmic signaling domain (SIRPα MT) had an increased amount of splenic marginal zone (MZ) B cells compared to wild-type controls. Immunohistochemical analysis revealed an increased localization of MZB cells into B cell follicular areas of the white pulp in SIRPα MT spleens. However, we found no signs of an increased MZB cell activation level in MT mice. The immune response to T-independent antigens in vivo was slightly increased in SIRPα MT mice while sorted MZB from these mice responded normally to LPS in vitro. Bone marrow reconstitution experiments demonstrated that the MZB cell phenotype of SIRPα MT mice was due to lack of SIRPα signaling in non-hematopoietic cells. In contrast, MZ retention of MZ macrophages required hematopoietic SIRPα, while normal distribution of metallophilic macrophages required non-hematopoietic SIRPα signaling. In summary, these data identified SIRPα signaling in non-hematopoietic cells to play an important role in regulating the numbers and positioning MZB cell in the spleen.
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Shrikant S
authors.initials: SS
authors.lastname: Kolan
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Boman
authors.affiliation: Department of Biochemistry and Molecular Biology, Division of Molecular and Cellular Signaling, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
authors.affiliation: Department of Clinical Microbiology, Division of Immunology, Umeå University, Umeå, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lejon
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden. Electronic address: per-arne.oldenborg@umu.se.
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic
keywords: B cell; Macrophage; Marginal zone; Spleen