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 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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-01, Vol.93 (1), p.221-225
Main Authors: Schröder, Anja E., Greiner, Axel, Seyfert, Christine, Berek, Claudia
Format: Article
Language:English
Subjects:
Adult
Aged
Arthritis
Arthritis, Rheumatoid - immunology
B lymphocytes
B-Lymphocytes - immunology
Base Sequence
Cell aggregates
Cell Differentiation
Clone Cells
DNA
Female
Gene Rearrangement, B-Lymphocyte
Germ cells
Humans
Immunologic Memory
Joints
Medical research
Molecular Sequence Data
Mutation
Nucleotides
Plasma cells
Rheumatism
Rheumatoid arthritis
Sequence Alignment
Sequence Homology, Nucleic Acid
Somatic mutation
Synovial membrane
Synovial Membrane - immunology
Synovial Membrane - pathology
T lymphocytes
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.1.221