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

• Published in: International immunology Vol. 21; no. 8; pp. 957 - 966
• Main Authors: Matheson, Louise S., Osborn, Michael J., Smith, Jennifer A., Corcos, Daniel, Hamon, Maureen, Chaouaf, Rima, Coadwell, John, Morgan, Geoff, Oxley, David, Brüggemann, Marianne
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2009; Oxford Publishing Limited (England)
• Subjects: Animals; B cell receptor; B-Lymphocytes - immunology; class-switch recombination; heavy chain disease; heavy-chain-only antibodies; Immunoglobulin A - biosynthesis; Immunoglobulin A - genetics; Immunoglobulin Class Switching; Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Immunoglobulin kappa-Chains - genetics; Immunoglobulin lambda-Chains - genetics; lymphocyte development; Mice; Mice, Knockout; Milk - immunology; Saliva - immunology; Spleen - immunology; heavy-chain-only antibodies; lymphocyte development; B cell receptor; heavy chain disease; class-switch recombination
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxp062

Recently, we identified that diverse heavy chain (H-chain)-only IgG is spontaneously produced in light chain (L-chain)-deficient mice (L−/− with silenced κ and λ loci) despite a block in B cell development. In murine H-chain IgG, the first Cγ 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 α 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 α chains lacking CH1 are released from the cell. This appears to be accomplished by imprecise class-switch recombination (CSR) from Sμ into the α constant region, which removes all or part of the Cα1 exon at the genomic level.