<strong>Native Tn only becomes an antigen when its protein no longer matches the protein of natural innate anti-Tn-reactive IgM</strong>

In view of the simultaneous formation of <em>Helix pomatia</em>-specific, Tn/serologically A-like glycolipids with germline-encoded anti-<em>Helix pomatia</em>-, Tn/A cross- reactive IgM in the ovary of a healthy and fertile mouse, it is suggested that the mammalian germline-encoded <em>Helix pomatia</em>-reactive IgM originates from a virtual native Tn, serologically A-like antigen, in which, for example, it is <em>O</em>-linked via its Fc regions and serine residues to a GalNAc epitope. It follows that native Tn only becomes an antigen when its protein no longer matches the protein of anti-Tn, exerted by innate natural IgM. However, native Tn/A is not present as a solid structure when the anti-Tn/A cross-reactive IgM is released into the plasma as a complementary protein during maturation, while the GalNAc molecule always provides the epitope, available for all internal and external, foreign and/or pathogenic proteins in Tn/A formation. In humans, this mechanism is compromised by the evolution of the ABO(H) blood group system, in which the phenotype-determining enzymes attenuate or neutralize the innate anti-H- and anti-Tn/A-reactive IgM, and making the ABO(H) phenotype an evolutionary selective trait.