Objective. To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vλ and Jλ gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation. Methods. Individual peripheral B cells from SS patients were analyzed for their Vλ gene usage by single-cell polymerase chain reaction amplification of genomic DNA and compared with those from normal controls. Results. Molecular differences from controls in Vλ-Jλ recombination were identified that were reflected by findings in the nonproductive Vλ repertoire of the patients, including enhanced rearrangement of Vλ10A and Jλ2/3 gene segments. In addition, a number of abnormalities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 Vλ genes (2A2, 2B2, 2C, and 7A), representing 56% of all productive Vλ rearrangements, was observed, suggesting positive selection of these genes. Overutilization of Jλ2/3 and underutilization of Jλ7 in both nonproductive and productive Vλ rearrangements of SS patients compared with controls suggested decreased receptor editing in SS. The mutational frequency did not differ from that in controls, and positive selection of mutations into the productive V gene repertoire was found, similar to that in controls, although mutational targeting toward RGYW/WRCY motifs, typically found in controls, was not found in SS patients. Conclusion. Disturbed regulation of B cell maturation with abnormal selection, defects in editing Ig receptors, and abnormal mutational targeting may contribute to the emergence of autoimmunity in SS.
|Original language||English (US)|
|Number of pages||13|
|Journal||Arthritis and rheumatism|
|State||Published - 2001|
ASJC Scopus subject areas
- Immunology and Allergy
- Pharmacology (medical)