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

Int Immunol. 2009 Aug;21(8):957-66. doi: 10.1093/intimm/dxp062. Epub 2009 Jun 26.

Abstract

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 Cgamma exon, C(H)1, 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 C(H)1 are released from the cell. This appears to be accomplished by imprecise class-switch recombination (CSR) from Smu into the alpha constant region, which removes all or part of the Calpha1 exon at the genomic level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • 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*
  • Mice
  • Mice, Knockout
  • Milk / immunology
  • Saliva / immunology
  • Spleen / immunology

Substances

  • Immunoglobulin A
  • Immunoglobulin Heavy Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains