Manipulation of the glycan-specific natural antibody repertoire for immunotherapy.
Natural immunoglobulin derived from innate-like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan-specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate-like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan-reactive B cell pool. Glycan-reactive natural antibodies (NAbs) have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan-reactive NAb repertoire is therefore paramount. A more thorough understanding of NAb repertoire development holds promise for the design of both biological diagnostics and therapies. In this article, we review the development and functions of NAbs and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in NAb repertoire development. We also discuss the implications of increased clonal plasticity of the innate-like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system.
['New|J Stewart|JS|', 'King|R Glenn|RG|', 'Kearney|John F|JF|']
D000818:Animals D000906:Antibodies D000917:Antibody Formation D000918:Antibody Specificity D000941:Antigens D016175:B-Lymphocyte Subsets D002454:Cell Differentiation D060966:Clonal Selection, Antigen-Mediated D000939:Epitopes D015322:Gene Rearrangement, B-Lymphocyte D006801:Humans D007113:Immunity, Innate D007167:Immunotherapy D064307:Microbiota D011134:Polysaccharides D013559:Symbiosis
natural antibody innate-like B lymphocyte repertoire development B-1 B cell clonotype glycan neodeterminant