Differential expression patterns of recombination-activating genes in individual mature B cells in juvenile idiopathic arthritis.
BACKGROUND
Re-expression of the recombination-activating genes (RAG) in peripheral B cells may be relevant in the development of autoreactive antibodies in autoimmune diseases. The presence of antinuclear antibodies (ANA) as a hallmark of oligoarticular juvenile idiopathic arthritis (o-JIA, early-onset type) indicates a breakdown in immunological tolerance.


OBJECTIVE
To examine the expression of RAG genes in peripheral blood mature B lymphocytes in patients with o-JIA.


METHODS
777 memory B cells from peripheral blood, CD19+ CD27+ CD5+ or CD19+ CD27+ CD5-, isolated from three ANA+ children with o-JIA and three healthy age-matched children, were examined for the expression of RAG1 and RAG2 mRNA. mRNA transcripts of activation-induced cytidine deaminase and immunoglobulin G were searched to further determine their developmental stage.


RESULTS
mRNA was present for any of the two RAG genes in the B cells of children with JIA and controls. However, the predominance of RAG1 or RAG2 was different. A significantly decreased frequency of RAG2-expressing memory B cells in both CD5+ and CD5- populations was noted in children with JIA (p<0.001), whereas the number of RAG1-expressing B cells was slightly increased. The coordinate expression of both the RAG genes was a rare event, similar in the CD5+ populations (1% in controls, 2% in children with JIA), but different among the CD5- compartments (5% v 0%; p<0.01).


CONCLUSIONS
These results argue for a reduced coordinate RAG expression in the peripheral CD5- memory B cells of patients with o-JIA. Thus, it was hypothesised that impaired receptor revision contributes to autoimmune pathogenesis in JIA.
Faber
C
C
Section of Paediatric Rheumatology and Osteology, Children's Hospital, University of Würzburg, Josef Schneider Str 2, D-97080 Würzburg, Germany.
Morbach
H
H
Singh
S K
SK
Girschick
H J
HJ
D001171:Arthritis, Juvenile / Q000235:genetics / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D018956:CD5 Antigens / Q000097:blood; D002478:Cells, Cultured; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D016654:Genes, RAG-1; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D007156:Immunologic Memory; D016130:Immunophenotyping; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C064658:RAG-1 protein; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase