Early ovariectomy reveals the germline encoding of the "natural" mammalian anti-A-reactive IgM reflecting developmental malignancy
The germline encoding of a non-immune immunoglobulin M (IgM) molecule in mammals was experimentally documented for the first time as a result of the specifically timed ovariectomy of C57BL/10 mice. The target of this innate antibody involves a trans-species developmental antigen that signifies malignancy when expressed in any non-developmental tissue. Although ovariectomy and castration result in uncontrolled and/or enhanced humoral and cellular immunity involving increased weights of the
... and thymus with pronounced B and T cell production, the development of mercaptoethanol-sensitive, complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after an ovariectomy that was performed in C57BL/10 mice prior to the onset of puberty. This non-immune murine anti-A, which is complementary to the trans-species, syngeneic ovarian GalNAc-glycan-bearing glycolipids and distinct from the cross-reactive adaptive anti-A antibody, was strongly downregulated or did not appear in plasma of animals ovariectomized at the age of 20 days. Thus, contrary to our previous view, this reactivity is unlikely to originate from a somatic, primary immune or autoimmune response. All of the murine tissues expressed the species-specific Forssman reactivity, and further A-like structures were identified in the male and female reproductive and endodermal organs by reaction with innate human anti-A antibody, while the murine anti-A was exclusively inhibited by syngeneic ovarian glycolipids. Moreover, the early ovarian tissue, which represents a last evolutionary and/or developmental location, showed a developmental polymorphism characterized by reactivity to the lectin from Dolichos biflorus and the agglutinin from Helix pomatia indicating the functional involvement of the O-GalNAc-determined mucin-type A-like, Tn- and Thomsen-Friedenreich (TF) epitopes that signify malignancy when accumulated and expressed in non-developmental tissues.