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Rheumatoid factor (RF) activity depends upon light chain somatic hypermutation (SHM), as well as particular heavy chain complementarity-determining region 3 (HCDR3) and light chain CDR3 combinations. A and B, Ig VH was paired with wild-type Ig Vκ for which some, all, or none of the SHMs were reverted to germline. C, Ig VH and Ig Vκ from RF from different patients were coexpressed and tested for RF activity. Swapping of Ig VH and Ig Vκ abrogated RF activity. Values are the mean ± SD.
