The enigma of IgE+ B-cell memory in human subjects

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 4; pp. 972 - 976
• Main Authors: Davies, Janet M., Platts-Mills, Thomas A., Aalberse, Rob C.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2013; Elsevier; Elsevier Limited
• Subjects: allergens; Allergens - immunology; Allergies; allergy; Allergy and Immunology; animal models; Animals; Antigens; B cells; B-lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Cell Differentiation - immunology; Cell Proliferation; epitopes; Epitopes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; germinal center; Germinal Center - immunology; Germinal Center - pathology; Humans; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - pathology; IgE; IgE+ B cells; Immune system; immunization; Immunoglobulin Class Switching; immunoglobulin E; Immunoglobulin E - immunology; immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Immunologic Memory; Immunopathology; Medical sciences; memory B cells; Mice; mites; phenotype; plasma cells; pollen; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; CDR; IgE+ B cells; PC; IgE; allergy; SHM; B cells; germinal center; memory B cells; plasma cells; GC; SIT; IgE + B cells; Plasma cell; Complementarity determining region; Somatic hypermutation; Allergen-specific immunotherapy; Human; Allergy; Immunopathology; Germinative center; Memory; B-Lymphocyte; Plasmocyte; Memory lymphocyte; Immunology
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2012.12.1569

Our understanding of the origin and fate of the IgE-switched B cell has been markedly improved by studies in mouse models. The immediate precursor of the IgE-switched B cell is either a relatively naive nonswitched B cell or a mature IgG-switched B cell. These 2 routes are referred to as the direct and indirect pathways, respectively. IgE responses derived from each pathway differ significantly, largely reflecting the difference in time spent in a germinal center and thus time for clonal expansion, somatic hypermutation, affinity maturation, and acquisition of a memory phenotype. The clinical and therapeutic implications for IgE responses in human subjects are still a matter of debate, largely because the immunization procedures used in the animal models are significantly different from classical atopic sensitization to allergens from pollen and mites. On the basis of the limited information available, it seems likely that these atopic IgE responses are characterized by a relatively low IgG/IgE ratio, low B-cell memory, and modest affinity maturation, which fits well with the direct switching pathway. It is still unresolved how the IgE response evolves to cover a wide epitope repertoire involving many epitopes per allergen, as well as many different allergens from a single allergen source.