Immunoglobulin V-lambda light chain gene usage in patients with Sjogren's syndrome

Objective. To determine whether patients with Sjogren's syndrome (SS) have abnormalities in Ig V-lambda and J(lambda) gene usage, differences in somat ic hypermutation, defects in selection, or indications for perturbations of B cell maturation. Methods. Individual peripheral B cells from SS patients were analyzed for t heir V-lambda gene usage by single-cell polymerase chain reaction amplifica tion of genomic DNA and compared with those from normal controls. Results. Molecular differences from controls in V-lambda-J(lambda) recombin ation were identified that were reflected by findings in the nonproductive V-lambda repertoire of the patients, including enhanced rearrangement of V( lambda)10A and J(lambda)2/3 gene segments. In addition, a number of abnorma lities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 V-lambda genes (2A2, 2B2, 2C, and 7A), repr esenting 56% of all productive V-lambda rearrangements, was observed, sugge sting positive selection of these genes. Overutilization of J(lambda)2/3 an d underutilization of J(lambda)7 in both nonproductive and productive V-lam bda rearrangements of SS patients compared with controls suggested decrease d receptor editing in SS. The mutational frequency did not differ from that in controls, and positive selection of mutations into the productive V gen e repertoire was found, similar to that in controls, although mutational ta rgeting toward RGYW/WRCY motifs, typically found in controls, was not found in SS patients. Conclusion. Disturbed regulation of B cell maturation with abnormal selecti on, defects in editing Ig receptors, and abnormal mutational targeting may contribute to the emergence of autoimmunity in SS.