A novel monospecific IgG2/lambda-autoantibody with specificity for a mitochondrial antigen: evidence for an antigen-driven pathogenetic B-cell response in rheumatoid synovial tissue, induced by tissue alteration.

To elucidate the pathogenic role of synovial B cells in rheumatoid arthritis (RA), nine human IgG/lambda-secreting B-cell hybridomas from rheumatoid synovial tissue of a patient with definite RA were screened by enzyme-linked immunosorbent assay and indirect immunofluorescence on tissue cryosections for detection of antibodies against autoantigens. One IgG2/lambda monoclonal antibody (mAb) from the B-cell hybridoma ELG211/15/63 (= hybr63) exhibited intense immunofluorescence reactivity in the cytoplasm of chondrocytes and epithelial cells of the gastrointestinal tract, especially in parietal cells of gastric mucosa (human and mouse tissue), representing a mitochondrial pattern. This result was confirmed by morphometric analysis of immunoelectron microscopy data, exhibiting a significantly higher labeling density in mitochondria (p < or = 0.

[Intra-articular B-cells in the pathogenesis of rheumatoid arthritis].

B-cells of the rheumatoid synovial tissue are constant and in some cases dominant elements of the inflammatory infiltrate and are located near to the site of tissue destruction. The pattern of B-cell distribution, the pattern and the relationship to the corresponding antigen presenting cells (follicular dendritical reticulum cells; FDC's) shows a great variation: B cells exhibit a follicular organisation forming secondary follicles, follicle like patterns with irregular formed FDC's networks and a diffuse pattern of and isolated FDC's. Molecular analysis of immunoglobulin genes from synovial B-cell clones and synovial tissue demonstrates the occurrence of immunoglobulin gene hypermutation as well as germline configuration.

Immunohistochemical analysis of proliferating and antigen-presenting cells in rheumatoid synovial tissue.

We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n = 21). The immunohistochemical detection of the proliferation-associated antigen Ki67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD68) antigen. Ki67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21).