Ontogeny of the autoimmune reaction in normal mice to antigens in erythrocytes and gut.

Normal mice have large numbers of cells (PFC) making antibody to an autoantigen which is exposed when their own erythrocytes are treated with proteolytic enzymes. Antibody against this antigen can be demonstrated in serum by haemolysis tests against the treated cells; this antibody rises to high levels within 2 to 3 days after injection of E. coli lipopolysaccharide. using quantitative absorption tests we have located the 'bromelain mouse' (BrM) autoantigen in the gastrointestinal tract as well as in erythrocytes; this distribution pattern resembles that of classical blood group antigens. We have described the ontogenetic development of PFC, B cells capable of activation by LPS, serum antibody and antigen. Free antigen is found in the gut shortly after birth. B cells rise rapidly to high levels in the peritoneal cavity, but require a short period of culture to release detectable antibody. PFC and B cells increase more slowly in spleen to adult levels by 3 weeks of age. The serum antibody lags behind PFC development. The pattern is consistent with an early stimulation of B cells in the peritoneal cavity by gut-derived antigen. We discuss the possible relationship of this autoimmune response to high natural responses against other autoantigens in mice, man and other species.