title: CD40, but not CD154, expression on B cells is necessary for optimal primary B cell responses.
abstract: CD40 is an important costimulatory molecule for B cells as well as dendritic cells, monocytes, and other APCs. The ligand for CD40, CD154, is expressed on activated T cells, NK cells, mast cells, basophils, and even activated B cells. Although both CD40(-/-) and CD154(-/-) mice have impaired ability to isotype switch, form germinal centers, make memory B cells, and produce Ab, it is not entirely clear whether these defects are intrinsic to B cells, to other APCs, or to T cells. Using bone marrow chimeric mice, we investigated whether CD40 or CD154 must be expressed on B cells for optimal B cell responses in vivo. We demonstrate that CD40 expression on B cells is required for the generation of germinal centers, isotype switching, and sustained Ab production, even when other APCs express CD40. In contrast, the expression of CD154 on B cells is not required for the generation of germinal centers, isotype switching, or sustained Ab production. In fact, B cell responses are completely normal when CD154 expression is limited exclusively to Ag-specific T cells. These results suggest that the interaction of CD154 expressed by activated CD4 T cells with CD40 expressed by B cells is the primary pathway necessary to achieve B cell activation and differentiation and that CD154 expression on B cells does not noticeably facilitate B cell activation and differentiation.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA.
authors.forename: Byung O
authors.initials: BO
authors.lastname: Lee
authors.forename: Juan
authors.initials: J
authors.lastname: Moyron-Quiroz
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.forename: Kim L
authors.initials: KL
authors.lastname: Kusser
authors.forename: Louise
authors.initials: L
authors.lastname: Hartson
authors.forename: Frank
authors.initials: F
authors.lastname: Sprague
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D016026:Bone Marrow Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009592:Nitrohydroxyiodophenylacetate / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011828:Radiation Chimera / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D018984:Epitopes, T-Lymphocyte; D023201:CD40 Ligand; D009592:Nitrohydroxyiodophenylacetate; D010047:Ovalbumin