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International Immunology Advance Access published online on June 26, 2009
International Immunology, doi:10.1093/intimm/dxp062
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Light chain-deficient mice produce novel multimeric heavy-chain-only IgA by faulty class switching

Louise S. Matheson*, Michael J. Osborn*, Jennifer A. Smith, Daniel Corcos, Maureen Hamon, Rima Chaouaf, John Coadwell, Geoff Morgan, David Oxley and Marianne Brüggemann

The Babraham Institute, Babraham, Cambridge CB22 3AT, UK

Correspondence to: M. Brüggemann; E-mail: marianne.bruggemann{at}bbsrc.ac.uk

Recently, we identified that diverse heavy chain (H-chain)-only IgG is spontaneously produced in light chain (L-chain)-deficient mice (L–/– with silenced {kappa} and {lambda} loci) despite a block in B cell development. In murine H-chain IgG, the first C{gamma} exon, CH1, is removed after DNA rearrangement and secreted polypeptides are comparable with camelid-type H-chain IgG. Here we show that L–/– mice generate a novel class of H-chain Ig with covalently linked {alpha} chains, not identified in any other healthy mammal. Surprisingly, diverse H-chain-only IgA can be released from B cells at levels similar to conventional IgA and is found in serum and sometimes in milk and saliva. Surface IgA without L-chain is expressed in B220+ spleen cells, which exhibited a novel B cell receptor, suggesting that associated conventional differentiation events occur. To facilitate the cellular transport and release of H-chain-only IgA, chaperoning via BiP association seems to be prevented as only {alpha} chains lacking CH1 are released from the cell. This appears to be accomplished by imprecise class-switch recombination (CSR) from Sµ into the {alpha} constant region, which removes all or part of the C{alpha}1 exon at the genomic level.

Keywords: B cell receptor, class-switch recombination, heavy chain disease, heavy-chain-only antibodies, lymphocyte development

* These authors contributed equally to this work.

Transmitting editor: D. Fearon

Received 10 December 2008, accepted 29 May 2009.


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