International Immunology, Vol. 14, No. 6, pp. 659-667,
June 2002
© 2002 Japanese Society for Immunology
Critical role of B cells in the development of T cell tolerance to aeroallergens
1 Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, CA 94305-5208, USA 2 Present address: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10034, USA
Correspondence to: D. T. Umetsu; E-mail: umetsu{at}stanford.edu
Transmitting editor: L. Lanier
Respiratory exposure to allergen induces the development of allergen-specific CD4+ T cell tolerance that effectively protects against the development of allergic-sensitization and Th2-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.
Keywords: allergy, asthma, B lymphocyte, lung, mucosa, suppression, tolerance
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