Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis.

TLDR

In rheumatoid arthritis, the synovial membrane is infiltrated by lymphoid cells that can form structures resembling germinal centers. The study directly isolated these infiltrates to assess whether B‑cell clones within them undergo selection and expansion analogous to germinal center processes in secondary lymphoid organs. The data indicate an antigen‑driven process that accumulates B cells in the synovial membrane, with identical sequences across sections suggesting memory B cells can proliferate without additional somatic mutations, intraclonal diversity underscoring a germinal center‑like character, and this represents the first demonstration of such a reaction outside lymphoid tissue.

Abstract

In patients with rheumatoid arthritis the synovial membrane of the affected joint is infiltrated with lymphoid cells which may be arranged in structures resembling germinal centers. We have directly isolated such infiltrates to determine whether B-cell clones within them are selected and expanded in a process analogous to that which normally takes place in the germinal centers in secondary lymphoid organs. The data suggest that an antigen-driven process leads to the accumulation of B cells in the synovial membrane. The finding of identical sequences in consecutive sections suggests that under conditions of chronic stimulation, memory B cells may enter a stage of differentiation in which they proliferate without further accumulation of somatic mutations. Further we see intraclonal diversity which underlines the germinal center-like character of these infiltrates and demonstrates that a microenvironment is built up in this nonlymphoid tissue which supports antigen-dependent differentiation of B cells. This is the first demonstration, to our knowledge, of a germinal center-like reaction outside lymphoid tissue.