Contribution of the V lambda light chain to the development of the primary antibody repertoire.
The experiments outlined here provide evidence that most VH gene families are expressed in association with either of three V lambda genes available in kappa-deficient mice, though their expression is nonrandom. An exclusive use of V lambda L-chain genes, where predominantly expressed V lambda 1 and V lambda 2 differ by only seven amino acid substitutions in the germline, results in a higher degree of self-reactive antibodies to conserved natural antigens like albumin, thyroglobulin, and stress proteins. The higher levels of self-reactive antibodies, characteristic of preimmune B-cell repertoire, are likely to be a product of nonrandom VH gene family expression and their restricted pairing with three V lambda L-chain genes. These data suggest that a low lambda L-chain expression in normal mice is due, in part, to endogenous selection against lambda L chain in order to restrict self reactivity within the homeostatic threshold.
D000818:Animals; D000916:Antibody Diversity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family
D001323:Autoantibodies; D001324:Autoantigens; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains