Selection of anti-double-stranded DNA B cells in autoimmune MRL-lpr/lpr mice

Ching Chen*, Hui Li, Qi Tian, Michael Beardall, Yang Xu, Nina Casanova, Martin Weigert

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Abs to DNA and nucleoproteins are expressed in systemic autoimmune diseases, whereas B cells producing such Abs are edited, deleted, or inactivated in healthy individuals. Why autoimmune individuals fail to regulate is not well understood. In this study, we investigate the sources of anti-dsDNA B cells in autoimmune transgenic MRL-lpr/lpr mice. These mice are particularly susceptible to lupus because they carry a site-directed transgene, H76R that codes for an anti-DNA H chain. Over 90% of the B cells are eliminated in the bone marrow of these mice, and the few surviving B cells are associated with one of two Vκ editors, Vκ38c and Vκ21D. Thus, it appears that negative selection by deletion and editing are intact in MKL-lpr/lpr mice. However, a population of splenic B cells in the H76R MRL-lpr/lpr mice produces IgG anti-nuclear Abs, and these mice have severe autoimmune organ damage. These IgG Abs are not associated with editors but instead use a unique Vκ gene, Vκ23. The H76R/Vκ23 combination has a relatively high affinity for dsDNA and an anti-nuclear Ab pattern characteristic of lupus. Therefore, this Vκ gene may confer a selective advantage to anti-DNA Abs in diseased mice.

Original languageEnglish (US)
Pages (from-to)5183-5190
Number of pages8
JournalJournal of Immunology
Volume176
Issue number9
DOIs
StatePublished - May 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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