Antigen-independent, IgM-induced antibody responses: requirement for "recurrent" idiotypes.

Anti-idiotypic antibodies (a-Id) were produced in syngeneic mice against two monoclonal IgM antibodies of BALB/c origin, TNP. 11 and SP/603. In plaque inhibition tests, using IgM-secreting hybridoma cells and anti-idiotypic antibodies, these two IgM proteins, as well as the anti-TNP myeloma protein MOPC 460 (IgA) were found to carry non-cross-reactive idiotypes. Analysis of the anti-trinitrophenyl (TNP) plaque-forming cells (PFC) in BALB/c mice, either normal or immunized with TNP-horse red blood cells, revealed that in addition to the MOPC 460 Id, also the SP/603 Id is recurrent and expressed by a fraction of the anti-TNP antibody-secreting cells in all individuals tested. In contrast, the TNP. 11 Id could not be detected in any BALB/c mouse studied. TNP. 11 and SP/603 antibodies were then characterized by their ability to induce an antigen-independent anti-TNP response in normal BALB/c mice. While TNP. 11 was found to be inactive, the same titers of SP/603 IgM induced antigen-specific PFC all of which expressed the SP/603 Id, and increased titers of circulating IgM molecules carrying the same Id, suggesting that "recurrent" but not "nonrecurrent" Id are competent in this respect. A fraction of these SP/603-induced, SP/603-positive anti-TNP antibodies also carried MOPC 460 Id, suggesting expression on the same molecule of idiotypic determinants found on independent non-cross-reactive "recurrent" idiotypes.