The germline encoding of a non-immune IgM molecule in mammals was experimentally documented for the first time by specifically timed ovariectomy of C57BL/10 mice, and the target of this innate antibody is a trans-species developmental antigen, which when expressed in any non-developmental tissue signifies malignancy. Although ovariectomy and castrations have been de­scribed to result in uncontrolled and/or enhanced humoral and cellular immunity, involving increasing weights of spleen and thymus

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... with pronounced B and T cell productions, the development of the mercaptoethanol-sensitive and complement-binding, non-immune anti-A reactivity in murine plasma was not enhanced after ovariectomy performed in C57BL/10 mice before the onset of puberty. This non-immune murine anti-A, which is complementary to trans-species, syngeneic ovarian GalNAc-glycan-bearing glycolipids and distinct from cross-reactive adaptive anti-A antibody, was strongly retarded or did not ap­pear at all in plasmas 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 murine tissues expressed the species-typical Forssman reactivity and further A-like structures were, by reaction with innate human anti-A antibody, identified in male and female reproductive and endodermal organs, 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 DBL and HPA reactivity indicating the functional involvement of O-GalNAc-determined mucin-type A-like Tn and TF epitopes that, when expressed by non-developmental tissues, signify malignancy.