title: gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory.
abstract: gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756.
authors.forename: T M
authors.initials: TM
authors.lastname: Foy
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: J A
authors.initials: JA
authors.lastname: Ledbetter
authors.forename: A
authors.initials: A
authors.lastname: Aruffo
authors.forename: E
authors.initials: E
authors.lastname: Claassen
authors.forename: R J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D005260:Female; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand