Early ovariectomy unmasking the non-somatic origin of murin anti-A-reactive IgM reflecting developmental malignancy
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
... f spleen and thymus 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.