title: Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas.
abstract: CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T-B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction.
authors.affiliation: Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bolduc
authors.forename: Eugene
authors.initials: E
authors.lastname: Long
authors.forename: Dale
authors.initials: D
authors.lastname: Stapler
authors.forename: Marilia
authors.initials: M
authors.lastname: Cascalho
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.forename: Michiko
authors.initials: M
authors.lastname: Shimoda
mesh_terms: D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D018985:Epitopes, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D023201:CD40 Ligand