Monoclonal antibodies to the idiotypic determinants of a human IgG paraprotein: evidence for complexity of the anti-idiotype response.

BALB/c mice were immunized with a human gamma 2k paraprotein and hybridomas prepared by the Kohler & Milstein technique. Ten hybridoma clones producing high levels of antibody competed reacting specificity with the immunogen were isolated. Six of the monoclonal antibodies competed strongly with each other for sites on the antigen. In reverse passive haemagglutination tests immunoglobulins reacting with the antibodies were not detectable in normal or pathological sera. Polyclonal antisera to two of the monoclonal antibodies were prepared in rabbits; they were rendered specific by adsorption with Sepharose-normal mouse IgG and tested against the other monoclonal antibodies. A weak cross-reaction of one of the mouse antibodies with the immunogen was observed with one antiserum but none with the other. Furthermore, no repetition of the idiotypes of the two immunogens was observed in polyclonal responses of BALB/c mice immunized with the same paraprotein antigen. These results with monoclonal antibodies confirm those obtained with polyclonal antisera in showing that the antibody response of one species to the private idiotype determinants of an immunoglobulin of another species is highly heterogeneous.