A minor group of rheumatoid factors isolated from a patient with rheumatoid arthritis is derived from somatically mutated Vk1 genes further evidence that rheumatoid factors during autoimmune diseases undergo an antigen driven maturation.

To better understand the structural basis for rheumatoid factor [RF] activity and the origin of auto-antibodies in human autoimmune diseases, we isolated the RF producing B cells from the peripheral blood and from the synovial fluid of a patient suffering from rheumatoid arthritis [RA]. We previously demonstrated that a significant fraction of these RF were derived from three VkIII genes known to encode most of the monoclonal RF light chain variable regions. To get more insight into the actual repertoire of RF-Vk genes during RA, we analyzed the nucleotide sequences of RF light chain variable regions of other Vk families. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from RF producing cells from the same patient KRA, we isolated only three different rearranged Vk-Jk complexes: slkv5, slkv7 and bkv42, all derived from VkI germ-line genes not previously known to be associated with RF activity; this suggests that the repertoire of VL genes coding for RF during RA is more d...