Figure 4.

At the site of disease, activated B cells are thought to possess a potent antigen-presenting capacity driving the expansion of effector T cells. The T cells implicated in the disease pathogenesis are cytotoxic CD4⁺ T cells (CD4⁺ CTL) rather than any traditional helper T cell subset seen in other rheumatologic diseases (i.e. Th1, Th17). CD4⁺ CTLs carry both cytotoxic and pro-fibrotic functions, the latter thought to occur by the secretion of transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ) and interleukin-1 beta (IL-1β). The resultant fibrosis takes a “storiform” pattern for unclear reasons and this conglomeration of activated B cells, CD4⁺ CTLs, and fibrosis forms the fibro-inflammatory lesions observed microscopically and tumefactive lesions observed clinically.

Key: CD = cluster of differentiation; CD4⁺ CTL = CD4⁺ cytotoxic T lymphocyte; SLAMF7 = signaling lymphocyte activating marker family 7; TGF-β = transforming growth factor-beta; IFN-γ = interferon-gamma, IL-1β = interleukin-1 beta.