title: Follicular dendritic cell secreted protein (FDC-SP) regulates germinal center and antibody responses.
abstract: We previously identified follicular dendritic cell secreted protein (FDC-SP), a small secreted protein of unknown function expressed in human tonsillar germinal centers (GC). To assess potential in vivo activities of FDC-SP, transgenic mice were generated to constitutively express FDC-SP in lymphoid tissues. FDC-SP transgenic mice show relatively normal development of immune cell populations, with the exception of a small increase in mature follicular B cells, and normal lymphoid tissue architecture. Upon immunization with a T-dependent Ag, FDC-SP transgenic mice were capable of producing an Ag-specific Ab; however, the titers of Ag-specific IgG2a and IgE were significantly reduced. GC responses after immunization were markedly diminished, with transgenic mice showing decreased numbers and sizes of GCs but normal development of follicular dendritic cell networks and normal positioning of GCs. FDC-SP transgenic mice also showed reduced production of Ag-specific IgG3 Ab after immunization with a type II T-independent Ag, suggesting that the FDC-SP can also regulate the induction of B cell responses outside the GC. Purified FDC-SP transgenic B cells function normally in vitro, with the exception of blunted chemotaxis responses to CXCL12 and CXCL13. FDC-SP can induce the chemotaxis of CD40-stimulated nontransgenic B cells and can significantly enhance B cell migration in combination with chemokines, indicating that FDC-SP may function in part by regulating B cell chemotaxis. These results provide the first evidence for immunomodulatory activities of FDC-SP and implicate this molecule as a regulator of B cell responses.
authors.affiliation: Department of Immunology, University of Manitoba, 703 William Avenue, Winnipeg, Manitoba, Canada.
authors.forename: Monther
authors.initials: M
authors.lastname: Al-Alwan
authors.forename: Qiujiang
authors.initials: Q
authors.lastname: Du
authors.forename: Sen
authors.initials: S
authors.lastname: Hou
authors.forename: Baher
authors.initials: B
authors.lastname: Nashed
authors.forename: Yijun
authors.initials: Y
authors.lastname: Fan
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Marshall
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000276:immunology; D002633:Chemotaxis; D020566:Dendritic Cells, Follicular / Q000276:immunology*; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; C465579:FDC secreted protein, mouse; D011506:Proteins