Ig λ and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation

Thomas Dörner, Nancy L. Farner, Peter E. Lipsky

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

To determine the distribution of Vλ and Jλ as well as V11 and J11 gene usage in a patient with systemic lupus erythematosus (SLE), productive and nonproductive VJ and V(D)J rearrangements were amplified from individual peripheral CD19+ B cells and were analyzed. No differences in the Vλ and Jλ or the V11 and J11 gene usage in the nonproductive gene repertoire of this SLE patient were found compared with the distribution of genes found in normal adults, whereas marked skewing of both Vλ and V11 was noted among the productive rearrangements. The distribution of productive Vλ rearrangements was skewed, with significantly greater representation of the Jλ distal cluster C VA genes and the Vλ distal Jλ7 element, consistent with the possibility that there was receptor editing of the Vλ locus in this patient. Significant bias in V11 gene usage was also noted with V113 family members dominating the peripheral B cell repertoire of the SLE patient (83%) compared with that found in normal subjects (55%; p < 0.001). Notably, a clone of B cells employing the V13-11 gene for the heavy chain and the Vλ1G segment for the light chain was detected. These data are most consistent with the conclusion that extreme B cell overactivity drives the initial stages of SLE leading to remarkable changes in the peripheral V gene usage that may underlie on fail to prevent the emergence of autoimmunity.

Original languageEnglish (US)
Pages (from-to)1027-1036
Number of pages10
JournalJournal of Immunology
Volume163
Issue number2
StatePublished - Jul 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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