title: Critical role of B cells in the development of T cell tolerance to aeroallergens.
abstract: Respiratory exposure to allergen induces the development of allergen-specific CD4(+) T cell tolerance that effectively protects against the development of allergic-sensitization and T(h)2-biased immunity. The establishment of T cell unresponsiveness to aeroallergens is an active process preceded by a transient phase of T cell activation that requires T cell co-stimulation and is critically influenced by the antigen-presenting cell type. In this study we examined the role of B cells in the development of respiratory tolerance following intranasal (i.n.) exposure to a prototypic protein antigen. We found that respiratory exposure of BCR-transgenic (Tg) mice to minute quantities of cognate antigen effectively induced T cell unresponsiveness, indicating that antigen presentation by antigen-specific B cells greatly enhanced the development of respiratory tolerance. In contrast, respiratory T cell unresponsiveness could not be induced in B cell-deficient JHD mice exposed to i.n. antigen, although T cell tolerance developed in JHD mice reconstituted with B cells, suggesting that B cells are required for the induction of respiratory T cell tolerance. Respiratory exposure of BCR-Tg mice to cognate antigen induced activation of antigen-specific T cells and partial activation of antigen-specific B cells, as demonstrated by enhanced expression by B cells of class II MHC and B7 molecules but lack of antibody secretion. Our data indicate that B cells critically influence the immune response to inhaled allergens and are required for the development of allergen-specific T cell unresponsiveness induced by respiratory allergen.
authors.affiliation: Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, CA 94305-5208, USA.
authors.forename: Daphne C
authors.initials: DC
authors.lastname: Tsitoura
authors.forename: V Pete
authors.initials: VP
authors.lastname: Yeung
authors.forename: Rosemarie H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D020545:Respiratory Mucosa / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D011947:Receptors, Antigen, B-Cell; D010047:Ovalbumin; D009113:Muramidase