Immunoglobulin kappa chain receptor editing in systemic lupus erythematosus.

Abstract

To determine whether receptor editing of Vkappa genes was involved in the pathogenesis of systemic lupus erythematosus (SLE), the usage of Vkappa and Jkappa gene elements from individual peripheral CD19(+) B cells obtained from a patient with untreated SLE was examined. No differences in the Vkappa and Jkappa gene usage in the nonproductive gene repertoire of this SLE patient were noted compared with the distribution of genes found in normal adults. However, an increased usage of Jkappa5 segments, and a significant overrepresentation of the Vkappa1 and Vkappa4 families, especially the L15, O14/O4, and B3 genes characterized the productive Vkappa gene repertoire of the SLE patient. Furthermore, Jkappa5-containing Vkappa gene rearrangements in the productive but not the nonproductive repertoire manifested significantly fewer mutations compared with Vkappa genes recombined with Jkappa1-4. These data are consistent with the conclusion that receptor editing of Vkappa is much more apparent in this SLE patient than in normals and suggest that a deficiency in this means to counteract the emergence of autoimmunity is not an essential feature of SLE.