Enhanced mutational activity of Vκ gene rearrangements in systemic lupus erythematosus

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

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

To determine the differential impact of somatic hypermutation and selective influences on the light chain repertoire in systemic lupus erythematosus (SLE), the frequency and pattern of somatic hypermutations were compared between the productive and nonproductive Vκ gene repertoire manifested by individual CD19+ B cells in a patient with SLE. The mutational frequency of nonproductive rearrangements in the SLE patient was significantly (P < 0.001) increased (3.7 x 10-2) compared to normals (4.8 x 10-3). Similarly, the mutational frequency of the productive Vκ rearrangements was also significantly increased in the SLE patient (2.8 x 10-2 vs 1.1 x 10-2) (P < 0.001). There were no differences in the R/S ratios of mutations in productive and nonproductive Vκ rearrangements. Moreover, a variety of mutational 'hot spots' were noted, but, unexpectedly, in the FRs. As in normals, mutations were found most frequently in RGYW/WRCY sequences accounting for 39.3% (nonproductive) and 40.1% (productive) of all mutations. Of note, nonproductive Vκ rearrangements harbored significantly more mutations than productive rearrangements (P < 0.05) indicating that there was overall selection against mutations in the expressed repertoire. This was most apparent in the CDR3. These data are most consistent with the conclusion that, in this SLE patient, the mutational machinery was markedly enhanced compared to normals, but with no subsequent positive selection of mutations. The enhanced mutational activity may play a role in the emergence of autoreactivity in this SLE patient.

Original languageEnglish (US)
Pages (from-to)188-196
Number of pages9
JournalClinical Immunology
Volume92
Issue number2
DOIs
StatePublished - Aug 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Enhanced mutational activity of Vκ gene rearrangements in systemic lupus erythematosus'. Together they form a unique fingerprint.

  • Cite this