Lambda light chain revision in the human intestinal IgA response.
Revision of Ab L chains by secondary rearrangement in mature B cells has the potential to change the specific target of the immune response. In this study, we show for the first time that L chain revision is normal and widespread in the largest Ab producing population in man: intestinal IgA plasma cells (PC). Biases in the productive and non-productive repertoire of lambda L chains, identification of the circular products of rearrangement that have the characteristic biases of revision, and identification of RAG genes and protein all reflect revision during normal intestinal IgA PC development. We saw no evidence of IgH revision, probably due to inappropriately orientated recombination signal sequences, and little evidence of kappa-chain revision, probably due to locus inactivation by the kappa-deleting element. We propose that the lambda L chain locus is available and a principal modifier and diversifier of Ab specificity in intestinal IgA PCs.
Su
Wen
W
Department of Immunobiology, Kings College London School of Medicine, Guy's King's College, St Thomas' Hospitals, London, United Kingdom.
Gordon
John N
JN
Barone
Francesca
F
Boursier
Laurent
L
Turnbull
Wayne
W
Mendis
Surangi
S
Dunn-Walters
Deborah K
DK
Spencer
Jo
J
D000916:Antibody Diversity; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics* / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics* / Q000276:immunology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin
D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D009687:Nuclear Proteins; C499311:RAG2 protein, human