Critical role of B cells in the development of T cell tolerance to aeroallergens (original) (raw)

Respiratory exposure to allergen induces the development of allergen-speci®c 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 in¯uenced 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-speci®c B cells greatly enhanced the development of respiratory tolerance. In contrast, respiratory T cell unresponsiveness could not be induced in B cell-de®cient 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-speci®c T cells and partial activation of antigen-speci®c 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 in¯uence the immune response to inhaled allergens and are required for the development of allergen-speci®c T cell unresponsiveness induced by respiratory allergen.