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* Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada;
Tumor Immunology Unit, Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; and
Department of Medical Microbiology and Infectious Disease, University of Manitoba, Winnipeg, Manitoba, Canada
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.
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1 This work was supported by operating grants from the Canadian Institutes of Health Research (CIHR) and infrastructure support from the Canadian Foundation for Innovation. M.A. was supported by a postdoctoral fellowship from the King Faisal Specialist Hospital and Research Centre and the University of Manitoba Faculty Fund. Q.D. was supported by a studentship from the CIHR National Training Program in Allergy and Asthma. B.N. was supported by a fellowship from the Manitoba Institute for Child Health. A.J.M. was supported by a CIHR New Investigator Award.
2 Address correspondence and reprint requests to Dr. Aaron J. Marshall, Department of Immunology, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada. E-mail address: marshall{at}ms.umanitoba.ca
3 Abbreviations used in this paper: GC, germinal center; FDC, follicular dendritic cell; FDC-SP, FDC secreted protein; NP, 4-hydroxy-3-nitrophenylacetyl; PNA, peanut hemagglutinin.
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