A high incidence of cross-reactive idiotypes among murine natural autoantibodies

Anti-idiotypic (anti-Id) antibodies were produced in rabbits against two natural monoclonal IgM autoantibodies (NmAb), D23 and E7, which exhibited a broad reactivity and were derived from fusions of spleen cells from adult unprimed BALB/c mice and nonsecreting myeloma cell lines. They were used to test the reactivities of 12 NmAb obtained from adult and newborn unprimed mice. Both anti-Id recognized cross-reactive idiotopes frequently shared by NmAb; 8 out of the 12 NmAb reacted with anti-IdD23, while 5 of them also reacted with anti-IdE7. All of the Id-bearing antibodies possessed widespread reactivity with structurally dissimilar self and nonself antigens. In most cases, their cross-reactive Id determinants seemed to be located outside of their antigen-binding sites. Furthermore, the presence in normal mouse sera of significant levels of D23 and E7 idiotopes correlated with the presence of natural antibody activity and was mainly associated with IgM and IgG2b fractions. Finally, D23 idiotope(s) were also found on induced murine anti-myosin antibodies. The high incidence of cross-reactive idiotopes found among NmAb produced by clones derived from different mice and their presence in normal BALB/c mouse serum Ig fractions suggest that families of germ-line genes may encode for at least a part of them.