TNF and rheumatoid arthritis: In turn, activation of tissue resident lymphocytes, either by fibroblasts or other cells in close proximity, induces surface expression of TNFα or LTα homotrimers to trigger TNFR2-driven non-canonical NF-κB activation and BAFF transcription in fibroblasts (Figure 2).107,153,154,196,301,303 These data suggest a tissue- or inflammation-driven epigenetic and post-transcriptional regulation program that differentiates RA synovial and dermal fibroblasts, and may partly account for the accumulation of B cells in affected joints but not unaffected skin of these patients.