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

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 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. © The Japanese Society for Immunology. 2009. All rights reserved.