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jem Home » 1995 Archive » 1 August » 182 (2): 541
Article

Light chain replacement: a new model for antibody gene rearrangement.

E L Prak, M Weigert
E L Prak
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M Weigert
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DOI: 10.1084/jem.182.2.541 | Published August 1, 1995
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Abstract

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.

© 1995 Rockefeller University Press
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Light chain replacement: a new model for antibody gene rearrangement.
E L Prak, M Weigert
Journal of Experimental Medicine Aug 1995, 182 (2) 541-548; DOI: 10.1084/jem.182.2.541

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The Journal of Experimental Medicine: 215 (4)

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April 2, 2018
Volume 215, No. 4

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