Light chain-deficient mice produce novel multimeric heavy-chain-only IgA by faulty class switching.
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.
Matheson
Louise S
LS
The Babraham Institute, Babraham, Cambridge, UK.
Osborn
Michael J
MJ
Smith
Jennifer A
JA
Corcos
Daniel
D
Hamon
Maureen
M
Chaouaf
Rima
R
Coadwell
John
J
Morgan
Geoff
G
Oxley
David
D
Brüggemann
Marianne
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D017578:Immunoglobulin Class Switching; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000276:immunology; D012463:Saliva / Q000276:immunology; D013154:Spleen / Q000276:immunology
D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains