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, Shig ella flexneri, or Yersinia enterocolitica. Although the mechanism unde rlying the induction of a chronic synovitis is unknown, the expression of HLA-B27 seems to play a crucial role in the etiology of the diseas e. Bacterial antigens induce a humoral immune response, but little is known about the impact of B cells on the inflammatory processes develo ping in the synovial membrane. Materials and Methods: Cryostat section s were prepared from the synovial tissue (ST) of patients with ReA and stained with antibodies specific for T, B, and follicular dendritic c ells. Lymphoid infiltrates were directly isolated by microdisection an d DNA was prepared from them. The rearranged V genes were amplified by polymerase chain reaction (PCR), cloned, and sequenced. Results: Hist ological staining showed that germinal, center-like structures develop in the ST of patients with ReA. B cells with a heterogenous repertoir e were isolated from these lymphoid infiltrates. The majority of V reg ions carried somatic mutations indicating that sequences are derived f rom memory B cells. Genealogical trees demonstrate clonal expansion an d 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 p rogress of the disease. Whether B cells are specific for the bacteria inducing the synovitis or for self-determinants present in the ST rema ins to be determined.