title: Follicular dendritic cell secreted protein FDC-SP controls IgA production.
abstract: Follicular dendritic cell secreted protein (FDC-SP) is a secreted peptide predominantly expressed in mucosal tissues. We previously reported that FDC-SP transgenic mice have altered B-cell responses to systemic immunization; however, the role of FDC-SP in mucosal immunity is unknown. Here, we report that FDC-SP functions in regulating immunoglobulin A production. FDC-SP transgenic mice show decreased IgA levels in serum, saliva, and bronchoalveolar lavage fluid. Reciprocally, FDC-SP-deficient mice show significantly increased IgA levels in serum and intestinal lavage, associated with accumulation of IgA+ cells in blood, bone marrow, Peyer's patches, and lymph nodes. FDC-SP-deficient mice generated higher titers of antigen-specific IgA but normal IgG1 responses upon immunization. Purified FDC-SP transgenic B cells generated decreased IgA responses to transforming growth factor β (TGFβ)+interleukin 5 (IL5) stimulation. Consistent with a direct effect of FDC-SP on B cells, recombinant FDC-SP suppressed B-cell IgA production in vitro. Six- to 14-month-old FDC-SP-deficient mice show IgA deposition in kidney glomeruli, which was associated with proteinuria and pathology consistent with mild IgA nephropathy (IgAN). Our results demonstrate a novel biological activity of FDC-SP in controlling B-cell IgA production and identify FDC-SP-deficient mice as a novel mouse model of IgAN.
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Landego
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Jayachandran
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: I W
authors.initials: IW
authors.lastname: Gibson
authors.affiliation: Biogen-Idec, Cambridge, Massachusetts, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ambrose
authors.affiliation: 1] Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada [2] Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Marshall
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000276:immunology; D056747:Immunomodulation / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics / Q000276:immunology; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C465579:FDC secreted protein, mouse; D007070:Immunoglobulin A; D007132:Immunoglobulin Isotypes; D011506:Proteins