title: The kappa immunoglobulin light chain repertoire of peripheral blood B cells in patients with juvenile rheumatoid arthritis.
abstract: The frequent appearance of antinuclear antibodies in patients with juvenile rheumatoid arthritis (JRA) indicates a loss of tolerance in B cell differentiation and/or activation. In this analysis, we were interested whether particular changes in the immunoglobulin light chain repertoire might exist in early-onset pauciarticular arthritis (EOPA) patients thereby potentially revealing distinct molecular patterns, which characterize defects in central tolerance mechanisms as well as an autoreactive peripheral B cell repertoire. Using single cell sorting and single cell PCR the distribution of Vkappa Jkappa rearrangements has been analyzed in individual naïve B cells of patients with EOPA-JRA and healthy individuals. The immunoglobulin kappa light chain repertoire of peripheral blood B cells in EOPA patients seems to be skewed to a decreased use of downstream Vkappa gene segments indicating increased events of secondary V(D)J-recombination. Another prominent molecular pattern in JRA B cells seem to be a restricted combination of Vkappa Jkappa rearrangements based on the predominant utilization of the Jkappa 1 and 2 gene segment. The current study indicates disturbances in the peripheral B cell pool in juvenile rheumatoid arthritis. The peripheral blood B cell pool of JRA patients did show molecular changes in the kappa light chain repertoire which, in part, could be a sequel of secondary V(D)J-recombination and of a molecular bias during immunoglobulin rearrangement in the bone marrow. Thus, B cell tolerance might be broken by more than one pathogenic mechanism.
authors.affiliation: Pediatric Rheumatology, Immunology and Infectious Diseases, Children's Hospital, University of Würzburg, Germany. Morbach_H@klinik.uni-wuerzburg.de
authors.forename: Henner
authors.initials: H
authors.lastname: Morbach
authors.forename: Petra
authors.initials: P
authors.lastname: Richl
authors.forename: Claudius
authors.initials: C
authors.lastname: Faber
authors.forename: Sunit K
authors.initials: SK
authors.lastname: Singh
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Girschick
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000032:analysis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064658:RAG-1 protein