Contribution of receptor editing to the antibody repertoire.
Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.
Casellas
R
R
Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA.
Shih
T A
TA
Kleinewietfeld
M
M
Rakonjac
J
J
Nemazee
D
D
Rajewsky
K
K
Nussenzweig
M C
MC
D000818:Animals; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000276:immunology*; D011995:Recombination, Genetic; D017634:Self Tolerance
D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2