Light chain replacement: a new model for antibody gene rearrangement

• Published in: The Journal of experimental medicine Vol. 182; no. 2; pp. 541 - 548
• Main Authors: Prak, E L, Weigert, M
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 01.08.1995
• Subjects: Animals; B-Lymphocytes - physiology; Base Sequence; DNA Primers - chemistry; Gene Rearrangement, B-Lymphocyte, Light Chain; Genes, Immunoglobulin; Hybridomas; Immunoglobulin kappa-Chains - genetics; Mice; Molecular Sequence Data; Recombination, Genetic
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.182.2.541

A functional B cell antigen receptor is thought to regulate antibody gene rearrangement either by stopping further rearrangement (exclusion) or by promoting additional rearrangement (editing). We have developed a new model to study the regulation of antibody gene rearrangement. In this model, we used gene targeting to replace the J kappa region with a functional V kappa-J kappa light chain gene. Two different strains of mice were created; one, V kappa 4R, has a V kappa 4-J kappa 4 rearrangement followed by a downstream J kappa 5 segment, while the other, V kappa 8R, has a V kappa 8-J kappa 5 light chain. Here, we analyze the influence of these functional light chains on light chain rearrangement. We show that some V kappa 4R and V kappa 8R B cells only have the V kappa R light chain rearrangement, whereas others undergo additional rearrangements. Additional rearrangement can occur not only at the other kappa allele or isotype (lambda), but also at the targeted locus in both V kappa 4R and V kappa 8R. Rearrangement to the downstream J kappa 5 segment is observed in V kappa 4R, as is deletion of the targeted locus in both V kappa 4R and V kappa 8R. The V kappa R models illustrate that a productively rearranged light chain can either terminate further rearrangement or allow further rearrangement. We attribute the latter to editing of autoantibodies and to corrections of dysfunctional receptors.