DIFFERENTIATION OF B-CELLS IN THE NONLYMPHOID TISSUE OF THE SYNOVIAL-MEMBRANE OF PATIENTS WITH RHEUMATOID-ARTHRITIS

In patients with rheumatoid arthritis the synovial membrane of the aff ected joint is infiltrated with lymphoid cells which may be arranged i n structures resembling germinal centers. We have directly isolated su ch infiltrates to determine whether B-cell clones within them are sele cted and expanded in a process analogous to that which normally takes place in the germinal centers in secondary lymphoid organs, The data s uggest that an antigen-driven process leads to the accumulation of B c ells in the synovial membrane, The finding of identical sequences in c onsecutive sections suggests that under conditions of chronic stimulat ion, memory B cells may enter a stage of differentiation in which they proliferate without further accumulation of somatic mutations. Furthe r we see intraclonal diversity which underlines the germinal center-li ke character of these infiltrates and demonstrates that a microenviron ment is built up in this nonlymphoid tissue which supports antigen-dep endent differentiation of B cells. This is the first demonstration, to our knowledge, of a germinal center-like reaction outside lymphoid ti ssue.