The use of single signal anergy to inactive pathological B cells in an antigen-specific manner is discussed. Cross-linking surface immunoglobulin, with a construct which contains oligovalent B cell epitopes on a non-immunogenic molecular framework can be used to inactivate the target B cells if the construct lacks T cells epitopes. An example of such a B cell toleragen is LJP 394, which inactivates anti-dsDNA-specific B cells in vivo in murine immunized and spontaneous disease models. The drug enhances survival and lowers renal pathology in BXSB mice. Appropriate definition of epitopes of pathological (auto) antibodies thus offers an opportunity for pharmacological intervention.