Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Plasma cells secreting IgG, M, and A abound in the synovium of patients with rheumatoid arthritis, yet their immunoglobulin repertoire and clonal relationship remain to be elucidated. Locally synthesized immunoglobulins probably contribute to the chronic joint inflammatory processes which are characteristic of these patients. To determine whether B lymphocyte proliferation contributes to the synovial plasma cell infiltrate, the clonality of IgG mRNA in individual synovial biopsies from an actively inflamed joint of patients with rheumatoid arthritis was investigated by a combination of cDNA length analysis and DNA sequencing. Particular sizes of immunoglobulin cDNA, detectable in subclasses 1, 3, or 4, were expressed in most synovial biopsies from one patient, suggesting their origin from expanded clones present in each biopsy. To prove a clonal relationship between recurrent cDNA lengths, immunoglobulin cDNA was cloned from three regions of synovium in three patients. The sequence of clones with a recurrent cDNA length was determined. An IgG3 clone found in most synovial biopsies of one patient was encoded by an unmutated copy of the V(H)1 gene, DP7. In contrast, IgG3 clones encoded by mutated versions of the V(H)3 gene DP49 or the V(H)4 gene DP63 were expanded in the other two patients. Different somatic mutants of these clones were isolated from different sites in these patients. The ratio of replacement/silent somatic mutations in these two families of clones suggests that the selective clonal expansion in the synovium of patients with rheumatoid arthritis is due to an antigen-driven immune response.

Original publication

DOI

10.1002/eji.1830270219

Type

Journal article

Journal

European journal of immunology

Publication Date

02/1997

Volume

27

Pages

476 - 485

Addresses

The Kennedy Institute, London, GB.

Keywords

Synovial Membrane, Synovial Fluid, Humans, Arthritis, Rheumatoid, Immunoglobulins, Immunoglobulin G, RNA, Messenger, Cloning, Molecular, Base Sequence, Gene Frequency, Molecular Sequence Data, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male