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Contribution of the V lambda light chain to the development of the primary antibody repertoire
A Nangpal1, J Knott, V Lipsanen
1Department of Veterinary Microbiology and Immunology, University of Guelph, Ontario, Canada.
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.
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.