Allelically included B cells with two specificities are eliminated in the periphery

Abstract

Event Abstract Back to Event Allelically included B cells with two specificities are eliminated in the periphery Leen Baudewijn1*, Susanne G. Sækmose2, Christoffer Dellgren1 and Torben Barington1 1 Odense University Hospital, Department of Clinical Immunology, Denmark 2 Næstved Hospital, Department of Clinical Immunology, Denmark The basis for monospecificity of B cells is allelic exclusion of immunoglobulin (Ig) heavy (H) and light (L) chain genes during early differentiation. Allelic exclusion at the IgH locus requires expression of the pre-B cell receptor containing the mu chain and an in-frame (“productive”) VDJ rearrangement from one of the two IgH alleles inhibiting further IgH gene recombination. We investigated to which extent mature human B cells carrying a frame-shift mutation in exon 1 of the mu gene (muCH1) express productive VDJ-CH1 transcripts originating from the mutant allele. According to the feedback inhibition model of allelic exclusion, 12 % of these B cells may carry two productive VDJ rearrangements –one that has been expressed but failed to assemble into a surface-expressed B cell receptor due to the mutation and one that has been expressed in a membrane bound mu chain and saved the B cell from elimination. It is possible that after antigen stimulation, class switch recombination might occur on both functionally rearranged alleles leading to generation of memory B cells with dual specificity thereby breaking allelic exclusion. We amplified, cloned and sequenced VDJ-CH1 transcripts from mature B cells from a heterozygous human carrying a frame-shift muCH1mutation. We analyzed 950 unique clones of which 90% contained a productive VDJ rearrangement. Less than 1 % of the functionally rearranged transcripts originated from the mutant allele. These data suggest counter-selection of “double producers” when they expand in the peripheral immune system. Keywords: Humans, allelic exclusion, B cell receptor, monospecificity, Gene Rearrangement, B-Lymphocyte, Heavy Chain, Immunoglobulin mu-Chains, Mutation, V(D)J Recombination Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Baudewijn L, Sækmose SG, Dellgren C and Barington T (2013). Allelically included B cells with two specificities are eliminated in the periphery. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00203 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Leen Baudewijn, Odense University Hospital, Department of Clinical Immunology, Odense, 5000, Denmark, lbaudewijn@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Leen Baudewijn Susanne G Sækmose Christoffer Dellgren Torben Barington Google Leen Baudewijn Susanne G Sækmose Christoffer Dellgren Torben Barington Google Scholar Leen Baudewijn Susanne G Sækmose Christoffer Dellgren Torben Barington PubMed Leen Baudewijn Susanne G Sækmose Christoffer Dellgren Torben Barington Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.