Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome.

TLDR

Salivary glands of Sjögren's syndrome patients contain germinal‑center‑like structures, but it is unclear whether their microenvironment can support a true germinal‑center response. The study proposes that germinal‑center‑type responses can be induced in non‑lymphoid target tissues of autoimmune diseases, building on similar findings in rheumatoid synovium. The authors cloned and sequenced rearranged Ig V genes from B cells isolated from labial salivary gland biopsies of two patients. Analysis of Ig V genes showed polyclonal clusters with few mutations, dominant hypermutated clones in separate clusters, no shared clones indicating limited migration, and mutation patterns consistent with antigen‑driven selection, confirming an antigen‑driven germinal‑center‑type B‑cell response in Sjögren's syndrome salivary glands.

Abstract

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.