Antigen-dependent B cell differentiation in the synovial tissue of a patient with reactive arthritis.
BACKGROUND
Reactive arthritis (ReA) can develop as a consequence of a bacterial infection with organisms such as Chlamydia trachomata, Shigella flexneri, or Yersinia enterocolitica. Although the mechanism underlying the induction of a chronic synovitis is unknown, the expression of HLA-B27 seems to play a crucial role in the etiology of the disease. Bacterial antigens induce a humoral immune response, but little is know about the impact of B cells on the inflammatory processes developing in the synovial membrane.


METHODS
Cryostat sections were prepared from the synovial tissue (ST) of patients with ReA and stained with antibodies specific for T, B, and follicular dendritic cells. Lymphoid infiltrates were directly isolated by microdisection and DNA was prepared from them. The rearranged V genes were amplified by polymerase chain reaction (PCR), cloned, and sequenced.


RESULTS
Histological staining showed that germinal, center-like structures develop in the ST of patients with ReA. B cells with a heterogenous repertoire were isolated from these lymphoid infiltrates. The majority of V regions carried somatic mutations indicating that sequences are derived from memory B cells. Genealogical trees demonstrate clonal expansion and diversification of the B cell repertoire in the ST.


CONCLUSIONS
The finding of local V-region diversification suggests that in the ST of patients with ReA, an antigen-driven, T cell-dependent differentiation of B cells occurs. This local B cell response may contribute to the progress of the disease. Whether B cells are specific for the bacteria inducing the synovitis or for self-determinants present in the ST remains to be determined.
Schröder
A E
AE
Deutsches Rheuma ForschungsZentrum, Berlin, Germany.
Sieper
J
J
Berek
C
C
D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology*; D016918:Arthritis, Reactive / Q000097:blood* / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D004274:DNA, Recombinant; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D008297:Male; D008969:Molecular Sequence Data; D000091402:Prohibitins; D017386:Sequence Homology, Amino Acid; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology*
D000942:Antigens, Bacterial; D004274:DNA, Recombinant; D007135:Immunoglobulin Variable Region; C000717331:PHB2 protein, human; D000091402:Prohibitins