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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.
S Hou, and
I Landego, and
N Jayachandran, and
A Miller, and
I W Gibson, and
C Ambrose, and
A J Marshall
June 2007,
Journal of immunology (Baltimore, Md. : 1950),
S Hou, and
I Landego, and
N Jayachandran, and
A Miller, and
I W Gibson, and
C Ambrose, and
A J Marshall
September 2002,
Journal of immunology (Baltimore, Md. : 1950),
S Hou, and
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N Jayachandran, and
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I W Gibson, and
C Ambrose, and
A J Marshall
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S Hou, and
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N Jayachandran, and
A Miller, and
I W Gibson, and
C Ambrose, and
A J Marshall
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S Hou, and
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N Jayachandran, and
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C Ambrose, and
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February 1998,
Journal of immunology (Baltimore, Md. : 1950),
S Hou, and
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S Hou, and
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S Hou, and
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S Hou, and
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