An antigen valence theory to explain the evolution and organization of the humoral immune response

The three modes of antibody production, natural, T independent (TI) and T dependent (TD) are conserved among vertebrate species suggesting an important role for each in protection against pathogens. Here, I use an artificial 'universe' to argue that the three modes of antibody production represent layers that evolved to deal optimally with antigens of different valence. Thus, the apparently more sophisticated TD response has not superseded the natural and TI components of the humoral immune response. Furthermore, the characteristic differences in isotype, somatic mutation and memory displayed by each antibody layer are appropriate for their targeted range of surface structures. It is also suggested that the TD and TI activation arms are at the extremes of a continuum, with signal integration of antigen and T cell-derived signals contributing to B cell decisions about isotype selection, proliferation and secretion that minimize the time to protection.