Immunoglobulin V_λ light chain gene usage in patients with Sjögren's syndrome

Objective. To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig V_λ and J_λ 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 V_λ 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 V_λ-J_λ recombination were identified that were reflected by findings in the nonproductive V_λ repertoire of the patients, including enhanced rearrangement of V_λ10A and J_λ2/3 gene segments. In addition, a number of abnormalities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 V_λ genes (2A2, 2B2, 2C, and 7A), representing 56% of all productive V_λ rearrangements, was observed, suggesting positive selection of these genes. Overutilization of J_λ2/3 and underutilization of J_λ7 in both nonproductive and productive V_λ 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.