ANALYSIS OF THE MOLECULAR-BASIS OF SYNOVIAL RHEUMATOID FACTORS IN RHEUMATOID-ARTHRITIS

The objective of this study was to better understand the molecular bas is of IgM rheumatoid factor in rheumatoid arthritis (RA). We recently generated 10 different monoclonal IgM RF (mRF) molecules isolated from the synovium of a single patient with Rk The heavy (H) and light chai n CL) variable region (V) genes of these 10 mRFs were cloned and seque nced. Six mRFs used kappa light chains and 4 mRFs used lambda light ch ains. Of particular interest, 8 of 10 heavy chains used the JH4 joinin g region gene, and all five VH4 heavy chains used the DK4 diversity re gion gene with the JH4. Four of the VH4 clones used the same germline gene, likely representing a novel but closely related germline gene to VH4.18, and may be clonally related because of the extensive homology in their heavy chain sequence. Two VH4 clones shared the same light c hain gene, V kappa IIIb kv325 (99% homology) and the same JK4 joining region gene, while three VH4 clones used two different Light chain gen es, an uncommon V kappa 4 and a V lambda 4 gene, respectively. In this RA patient, there was recurrent utilization of VH4-DK4-21/10-JH4 gene s and a recurring association with gene elements V kappa 3 and V lambd a 4. Recurring usage of V kappa 3 (kv325) and V lambda 4 (lv418) gene elements may result from a light chain editing process whereby immatur e autoreactive B cells encountering self-antigen attempt, and often su cceed, in altering their specificities through secondary Ig light chai n gene rearrangement. Moreover, the oligaclonality of these RFs sugges t clonal relatedness secondary to an antigen-driven response. (C) 1997 Academic Press.