The power of the third dimension: Tissue architecture and autoimmunity in rheumatoid arthritis

Lymphoid organs are the anatomic solution to the challenge of responding to minute amounts of antigen with powerful effector mechanisms. By arranging interacting cells in complex three-dimensional topographies lymphoid organs provide an optimal match between form and function. This principle is exploited in ectopic lymphoid structures that characteristically appear in rheumatoid synovitis. Synovial tissue T cells and B cells cooperate in different types of lymphoid organizations. Dendritic cell networks in the inflamed synovial membrane optimize antigen collection, storage, processing, and presentation. Synovial tissue cells participate in lymphocyte recruitment and the formation of tissue architectures that amplify immune responses. Recent data support the concept that the tissue organization in the rheumatoid joint fosters a breakdown in self-tolerance by promoting a phase transition from self-limited immune responses to self-perpetuating autoimmune responses.