Rheumatoid factor isotype switch and somatic mutation variants within rheumatoid arthritis synovium
| Autor: | D G, Williams, S P, Moyes, R A, Mageed |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Aged
80 and over B-Lymphocytes Base Sequence Molecular Sequence Data Synovial Membrane Enzyme-Linked Immunosorbent Assay Original Articles Middle Aged Immunoglobulin Class Switching Polymerase Chain Reaction Immunoglobulin A Arthritis Rheumatoid Immunoglobulin M Rheumatoid Factor Sequence Homology Nucleic Acid Mutation Humans Electrophoresis Polyacrylamide Gel Female Amino Acid Sequence RNA Messenger Immunoglobulin Heavy Chains Sequence Alignment Aged |
| Zdroj: | Immunology. 98(1) |
| ISSN: | 0019-2805 |
| Popis: | The presence of clonally-related B-lymphocyte aggregates within synovial lining tisue of rheumatoid arthritis (RA) patients suggests a germinal centre-like reaction, which may hold implications for disease pathogenesis and the causes of chronic inflammation. We studied 250 rheumatoid factor (RF) heavy-chain sequences cloned from the synovium of three patients with RA, to determine whether they undergo both somatic mutation and isotype switching consistent with this hypothesis. Size analysis of immunoglobulin heavy-chain cDNAs from synovial RF+ B cells revealed oligoclonal RF+ populations and identically-sized VH-D-JH transcripts of different immunoglobulin isotypes. Sequencing of individual inserts selected from cloned immunoglobulin heavy-chain cDNAs demonstrated a clonal relationship between immunoglobulin M (IgM) RF and IgA RF, suggesting that this isotype switch occurred in synovium. Furthermore, most somatic mutations were found to have occurred after this isotype switch. This finding suggests that the RA synovial microenvironment sustains somatic mutation and isotype switching in RF-specific B lymphocytes akin to secondary lymphoid organs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|