Abstract
The origin of diversity of antibodies directed to a variety of antigens, as well as against a given defined determinant, not only in an outbred population but also within inbred strains, has been the subject of much discussion. When we consider where immunoglobulin (Ig) diversity might be generated during the life of an individual, there are clearly two stages during which such events could occur: (1) Stem-cell proliferation and development into cells that are committed to the B-cell lineage, i.e., expressing genes for an Ig molecule and other B-cell markers. (2) After the cells have expressed Ig receptors, they become antigen-sensitive, and further proliferation ensues on antigen contact and appropriate cell-cell interactions. It has been suggested that the affinity changes frequently associated with prolonged immunization can be assigned to generation of variability of antibody during the antigen-driven expansion of individual antibody-forming cell clones (Cunningham 1974), and that T cells may...
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