Light chain variable (V-L) sequences of rheumatoid factors (RF) in patients with primary Sjogren's syndrome (pSS): Moderate contribution of somatic hypermutation

We have characterized and sequenced the variable (V) region genes of the li ght (L) chains of 10 immunoglobulin (IgM) rheumatoid factor (RF) monoclonal antibodies (MoAb) derived by the hybridoma/Epstein-Barr virus (EBV) techni que from the peripheral blood of patients with primary Sjogren's syndrome ( pSS). Six out of 10 RFs used lambda (lambda) L chains, while four RFs used kappa (kappa) L chains. Five out of the six lambda RFs were encoded by V(la mbda)3 gene segments, the sixth one was encoded by a V(lambda)1 gene segmen t. This preferential utilization of the V(lambda)3 family genes suggests se lective expansion of the B cell in pSS. Three of the kappa RFs used V(kappa )3 gene segments, while the fourth used a V(kappa)2 gene segment. Half of t he RFs were found as unmutated copies of their closest germline (GL) gene. Interestingly these RFs were previously shown to use heavy (H) chains in GL gene configuration. Three RFs have very few mutations (2-3) and only two R Fs have substantial numbers of mutations (6 and Il). This also correlated w ith the number of mutations in the respective H chains. In contrast to RFs in normal and RA these results further suggest the somatic mutation to be o f moderate importance in the generation of RF from the peripheral blood of pSS patients.