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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

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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