Our previous studies of anti-DNA antibodies in SLE have demonstrated a preferential use of V kappa I and V lambda II gene families to encode light chains of antibodies that express the anti-DNA-associated 3I and 8.12 idiotypes, respectively. In this study, we employed PCR to obtain V kappa I and V lambda II germline genes from lupus patients in order to compare the germline genes to genes encoding expressed V kappa I and V lambda II light chains and to analyze the extent of somatic mutation among autoantibodies that derive from these light chain families. Our analysis shows that the germline repertoire among all persons (autoimmune and healthy) is comparable and that somatic mutation is used to diversify autoantibodies as well as anti-microbial antibodies. We have observed that autoantibodies encoded by V kappa I and V lambda II genes have a higher number of amino acid replacements in CDRs than autoantibodies encoded by other VL gene families. In addition, there may be subtle differences in V gene usage that distinguish the V kappa I-encoded light chains from other expressed V kappa light chains.