title: Immunoglobulin Vlambda light chain gene usage in patients with Sjögren's syndrome.
abstract: OBJECTIVE
  To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vlambda and Jlambda 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 Vlambda 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 Vlambda-Jlambda recombination were identified that were reflected by findings in the nonproductive Vlambda repertoire of the patients, including enhanced rearrangement of Vlambda10A and Jlambda2/3 gene segments. In addition, a number of abnormalities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 Vlambda genes (2A2, 2B2, 2C, and 7A), representing 56% of all productive Vlambda rearrangements, was observed, suggesting positive selection of these genes. Overutilization of Jlambda2/3 and underutilization of Jlambda7 in both nonproductive and productive Vlambda 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Hospital Charite, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kaschner
authors.forename: A
authors.initials: A
authors.lastname: Hansen
authors.forename: A
authors.initials: A
authors.lastname: Jacobi
authors.forename: K
authors.initials: K
authors.lastname: Reiter
authors.forename: N L
authors.initials: NL
authors.lastname: Monson
authors.forename: M
authors.initials: M
authors.lastname: Odendahl
authors.forename: G R
authors.initials: GR
authors.lastname: Burmester
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: T
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005434:Flow Cytometry; D005784:Gene Amplification; D018628:Gene Dosage; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D007144:Immunoglobulin J-Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains