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Follicular dendritic cell secreted protein FDC-SP controls IgA production.
Hou, S; Landego, I; Jayachandran, N; Miller, A; Gibson, I W; Ambrose, C; Marshall, A J.
Afiliación
  • Hou S; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Landego I; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Jayachandran N; Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Miller A; Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Gibson IW; Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.
  • Ambrose C; Biogen-Idec, Cambridge, Massachusetts, USA.
  • Marshall AJ; 1] Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada [2] Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, Canada.
Mucosal Immunol ; 7(4): 948-57, 2014 Jul.
Article en En | MEDLINE | ID: mdl-24399151
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 ß (TGFß)+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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina A / Proteínas / Formación de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina A / Proteínas / Formación de Anticuerpos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2014 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos