Diversity of Ig V gene segments found in anti-DNA autoantibodies from a single (NZB x NZW)F1 mouse.

Abstract

We have studied 18 anti-DNA secreting hybridomas derived from a single, nephritic NZB/NZW mouse. The antibodies were analyzed for the expression of idiotypic families that are enriched in the antibodies to DNA from diseased animals (IdGN2 and IdX), and for the expression of VH and V kappa gene segment subfamilies. Most of the mAb have characteristics similar to those that may be pathogenic because they 1) bound to native DNA, 2) were of the IgG2a or IgG2b isotype, and 3) expressed idiotopes associated with glomerulonephritis in NZB/NZW mice and human lupus. Among the 18 mAb, at least six VH subfamilies and six V kappa subfamilies were expressed. A majority of the antibodies utilized a VH gene segment from the large J558 subfamily. Slot blot analyses of total spleen cell RNA revealed that as NZB/NZW mice aged and developed nephritis, they expressed progressively higher quantities of Ig transcripts. The proportion of these transcripts derived from the VH J558 subfamily also increased. Our results indicate that a diversity of B cell clones participate in the anti-DNA response of a single NZB/NZW mouse. There was no preferential utilization of 3' Ig V gene segment subfamilies. Furthermore, there was no marked difference in the pattern of VH and V kappa gene segment expression in antibodies defined by their isotypes or idiotopes.