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Mol Immunol. 2008 Aug;45(14):3840-6. doi: 10.1016/j.molimm.2008.05.011. Epub 2008 Jul 9.

The kappa immunoglobulin light chain repertoire of peripheral blood B cells in patients with juvenile rheumatoid arthritis.

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  • 1Pediatric Rheumatology, Immunology and Infectious Diseases, Children's Hospital, University of Würzburg, Germany. Morbach_H@klinik.uni-wuerzburg.de

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.

PMID:
18614233
[PubMed - indexed for MEDLINE]
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