We have been studying the correlation between reactivity of human monoclonal antibodies with the variable region genes utilized by these antibodies. We analyzed a panel of low and high affinity antibodies generated from autoimmune and healthy individuals. Sequence analysis of the genes encoding variable regions of polyreactive antibodies either from autoimmune or from healthy subjects revealed that they are in germline configuration suggesting that they came from the normal B-cell repertoire. In contrast, the monoreactive antibodies show somatic point mutations suggesting that they came from antigen-driven cells.
