Cutting edge: CD40 ligand is a limiting factor in the humoral response to T cell-dependent antigens.
CD40 ligand (CD40L) plays a crucial role in T cell-dependent B cell responses, but whether its abundance is a limiting factor in their development is unclear. This question was addressed in transgenic mice expressing the murine CD40L gene under the control of the IL-2-promoter (CD40Ltg+). The fraction of activated T cells from the CD40Ltg+ mice with detectable levels of surface CD40L was modestly greater (1.1- to 2-fold) than littermate controls and paralleled an approximately 1.8-fold increase in CD40L mRNA abundance. In response to trinitrophenol (TNP)-keyhole limpet hemocyanin and tetanus/diphtheria vaccine, CD40Ltg+ mice developed higher titers of high-affinity IgG and IgG1 Ab than wild-type mice. In contrast, the Ab response of CD40Ltg+ and control mice was similar in response to the T-independent Ag TNP-Ficoll. These results suggest that a modest increment in expression of CD40L accelerates the development of T-dependent responses, and that CD40L plays a limiting role in the induction of high-affinity Ab and Ab-class switching.
Department of Immunology, University of Washington, Seattle 98195, USA.
M
M
Pérez-Melgosa
D
D
Hollenbaugh
C B
CB
Wilson
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000097:blood; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010851:Picrates / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology
D000955:Antigens, T-Independent; D019013:CD40 Antigens; D006241:Haptens; D007075:Immunoglobulin M; D008024:Ligands; D008562:Membrane Glycoproteins; D010851:Picrates; C020529:TNP-ficoll; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; D023201:CD40 Ligand; D005362:Ficoll; D006433:Hemocyanins