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From the forehead of Zeus: the ontogeny of the immune response
1Institute of the History of Medicine, Johns Hopkins University, Baltimore, MD 21204, USA.
Many of the most important developments that result in a fully functioning vertebrate immune system take place in the developing fetus. From a variety of gene segments there is assembled in B cells a congeries of antibody combining sites, one to a cell, which form the greater part of the large repertoire of immunological specificities that characterise the system. This capability is further expanded later by somatic mutations. Just as immunoglobulin isotypes are produced sequentially (IgM, IgD, IgG, IgE, IgA) as they are read along the chromosome, so does the fetus and neonate manifest immunological competence sequentially to different antigens by employing variable region germline genes as they appear along the chromosome. The generation of T cell receptor diversity is accomplished by a similar mechanism of gene segment translocations. Each stage in the lineage of T and B cells is associated with the appearance of unique combinations of surface molecular markers, which in T cells characterise also the specialised functions of different subsets. If the immune system does not spring forth quite fully formed from the evolved vertebrate genome, as Athena did from the forehead of Zeus, ontogenetic mechanisms have made it very nearly complete.
Many of the most important developments that result in a fully functioning vertebrate immune system take place in the developing fetus. From a variety of gene segments there is assembled in B cells a congeries of antibody combining sites, one to a cell, which form the greater part of the large repertoire of immunological specificities that characterise the system. This capability is further expanded later by somatic mutations. Just as immunoglobulin isotypes are produced sequentially (IgM, IgD, IgG, IgE, IgA) as they are read along the chromosome, so does the fetus and neonate manifest immunological competence sequentially to different antigens by employing variable region germline genes as they appear along the chromosome. The generation of T cell receptor diversity is accomplished by a similar mechanism of gene segment translocations. Each stage in the lineage of T and B cells is associated with the appearance of unique combinations of surface molecular markers, which in T cells characterise also the specialised functions of different subsets. If the immune system does not spring forth quite fully formed from the evolved vertebrate genome, as Athena did from the forehead of Zeus, ontogenetic mechanisms have made it very nearly complete.