Figure 5. Model of Blood and Synovial Gene-Expression Changes before and during Rheumatoid Arthritis Flares.

Inflammatory signals activate naive B cells (AC2), which in turn activate PRIME cells (AC3); these cells harbor the signature of synovial sublining fibroblast genes. According to this model, PRIME cells demarginate and are increased in blood before a flare and then decrease just after symptom onset; these cells or their progeny are increased in inflammatory synovium in patients with rheumatoid arthritis, where they contribute to and may be sufficient to cause joint inflammation.