| First Author | Hou S | Year | 2014 |
| Journal | Mucosal Immunol | Volume | 7 |
| Issue | 4 | Pages | 948-57 |
| PubMed ID | 24399151 | Mgi Jnum | J:307007 |
| Mgi Id | MGI:6708995 | Doi | 10.1038/mi.2013.113 |
| Citation | Hou S, et al. (2014) Follicular dendritic cell secreted protein FDC-SP controls IgA production. Mucosal Immunol 7(4):948-57 |
| abstractText | 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 beta (TGFbeta)+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. |
