Critical role of B cells in the development of T cell tolerance to aeroallergens

• Published in: International immunology 2002-06, Vol.14 (6), p.659-667
• Main Authors: Tsitoura, Daphne C, Yeung, V Pete, DeKruyff, Rosemarie H, Umetsu, Dale T
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Allergens - administration & dosage; Animals; Antibody Formation; B-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - immunology; Immune Tolerance; Immunity, Mucosal; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Muramidase - administration & dosage; Muramidase - immunology; Ovalbumin - administration & dosage; Ovalbumin - immunology; Receptors, Antigen, B-Cell - genetics; Respiratory Mucosa - immunology; T-Lymphocytes - immunology
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxf032

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.