Cell-cell interactions in synovitis. Interactions between T cells and B cells in rheumatoid arthritis

Abstract

In rheumatoid arthritis, T cells and B cells participate in the immune responses evolving in the synovial lesions. Interaction between T cells and B cells is probably antigen specific because complex microstructures typical of secondary lymphoid organs are generated. Differences between patients in forming follicles with germinal centers, T-cell-B-cell aggregates without germinal center reactions, or loosely organized T-cell-B-cell infiltrates might reflect the presence of different antigens or a heterogeneity in host response patterns to immune injury. Tertiary lymphoid microstructures in the rheumatoid lesions can enhance the sensitivity of antigen recognition, optimize the collaboration of immunoregulatory and effector cells, and support the interaction between the tissue site and the aberrant immune response. The molecular basis of lymphoid organogenesis studied in gene-targeted mice will provide clues to why the synovium is a preferred site for tertiary lymphoid tissue. B cells have a critical role in lymphoid organogenesis. Their contribution to synovial inflammation extends beyond antibody secretion and includes the activation and regulation of effector T cells.

Figure 1

The formation of lymphoid microstructures by T cells and B cells in rheumatoid synovitis. T cells and B cells infiltrating the synovial membrane are arranged into highly organized structures. Synovial lymphoid microstructures include two mutually exclusive types of T-cell–B-cell clusters, those lacking GCs (a, c) and follicles with central GCs (b, d). In both microstructures, T cells and B cells are mixed in a well-maintained ratio. Centroblasts and centrocytes in the follicular sample indicate a GC reaction that is missing from the aggregate sample. The stain in (a) and (b) was hematoxylin. CD23-expressing FDC networks were detected by immunoperoxidase technique with 3',3'-diaminobenzidine tetrahydrochloride substrate (c, d). Centers of follicles with GCs were occupied by FDC networks, reminiscent of typical secondary follicles in lymph nodes. No FDCs were identified in T-cell–B-cell aggregates that lacked GCs. It is not known whether synovial T-cell–B-cell aggregates resemble structures represented in secondary lymphoid tissues.

Figure 2

Schematic model of specialized cell populations and chemokines instrumental in the formation of GCs in secondary and tertiary lymphoid tissues. B_CB, centroblastic B cell; B_CC, centroclastic B cell; B_M, memory B cell; B_P, plasma B cell; DC, dendritic cell; HEV, high endothelial venule; T_N, naïve T cell; T_P, primed T cell.