Shared idiotypes and restricted VH genes among murine autoantibodies of various specificities

The autoantibodies studied here express cross-reactive idiotypes despite the fact that they are heterogeneous with respect to combining site. Furthermore, the presence of cross-reactive idiotypes is independent of the major histocompatibility complex, VH gene usage, and isotype. Similarly, VH gene usage shows that autoantibodies are derived from a restricted number of VH gene families. This restriction is independent of antigen specificity as well as the method of induction (i.e., spontaneous vs. induction). The observation that the VH 7183 gene is predominantly used suggests that certain autoantibodies may be derived from a unique set of B cells such as the Ly1+ B cells. It has been reported that these B cells secrete a high percentage of IgM autoantibodies. The studies reported here may provide greater insight into the genetic and immunoregulatory mechanisms by which autoantibodies arise. The precise mechanisms are not known but may involve both molecular (i.e., VH gene usage) and extracellular (i.e., idiotypic recognition) events.