Critical role of B cells in the development of T cell tolerance to aeroallergens
- 1 June 2002
- journal article
- Published by Oxford University Press (OUP) in International Immunology
- Vol. 14 (6), 659-667
- https://doi.org/10.1093/intimm/dxf032
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.Keywords
This publication has 34 references indexed in Scilit:
- Regulation of the IgE isotype switch: new insights on cytokine signals and the functions of ε germline transcriptsCurrent Opinion in Immunology, 2000
- B Lymphocytes Regulate Dendritic Cell (Dc) Function in VivoThe Journal of Experimental Medicine, 2000
- IMMUNOLOGIC BASIS OF ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESSAnnual Review of Immunology, 1999
- Aerosol-induced Immunoglobulin (Ig)-E Unresponsiveness to Ovalbumin Does Not Require CD8+ or T Cell Receptor (TCR)-γ/δ+ T Cells or Interferon (IFN)-γ in a Murine Model of Allergen SensitizationThe Journal of Experimental Medicine, 1998
- Th1 and Th2 CD4+ cells in human allergic diseasesJournal of Allergy and Clinical Immunology, 1997
- CD4+ T cell activation and tolerance induction in B cell knockout mice.The Journal of Experimental Medicine, 1996
- Successful T cell priming in B cell-deficient mice.The Journal of Experimental Medicine, 1995
- A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation.The Journal of Experimental Medicine, 1994
- Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens.The Journal of Experimental Medicine, 1992
- Clonal Expansion Versus Functional Clonal Inactivation: A Costimulatory Signalling Pathway Determines the Outcome of T Cell Antigen Receptor OccupancyAnnual Review of Immunology, 1989