A family of monoclonal antibodies (MoAb) was derived from the somatic cell fusion of P3NS1 myeloma cells and lymphoid cells from naturally infected mice of hyperimmunized mice. C57BL/6 mice were naturally infected with Schistosoma japonicum, and BALB/c mice were hyperimmunized with preparations of S. japonicum soluble egg antigens (SEA). The MoAbs which reflected the immune repertoire of naturally infected animals versus hyperimmune animals were characterized with regard to antibody isotype, antigen binding specificity, in-vitro immunosuppression of antigen-induced cell-mediated immune responses and the expression of SJ-CRIM, a major cross-reactive idiotype which appears on polyclonal anti-SEA antibodies generated during murine S. japonicum infection. The data indicate that for MoAbs of the IgG isotype which bound SEA by ELISA, the most immunosuppressive anti-SEA MoAbs identified expressed SJ-CRIM and were derived from naturally infected mice. All anti-SEA MoAbs expressing SJ-CRIM showed an identical banding pattern on immunoblot analysis which was abrogated by weak periodate treatment. The generation of expression of SJ-CRIM on MoAbs using differing methodologies across an allotype barrier indicates that the expression of SJ-CRIM is encoded by a germline gene. These data indicate an association between expression of this germline interstrain cross-reactive idiotype and immunosuppressive capacity. In addition, the immunoregulatory network which develops during immune S. japonicum infection is initiated by a carbohydrate epitope(s) found on various SEA. These data have profound implications in the use of the cross-reactive idiotype as a serodiagnostic tool in schistosomiasis.