Concepts for the development of a quantitative theory of clonal selection and class regulation using lessons from the original.

When Burnet wrote his modification of Jerne's theory he simply wrote-'It is postulated that when antigen-(receptor) contact takes place on the surface of a lymphocyte the cell is activated to settle in an appropriate tissue... and there undergo proliferation to produce a variety of descendants'.(1) But studies of 'activation' and 'proliferation' following receptor contact have turned out to be surprisingly complex-much more complex than the theory apparently requires. It is timely, on this 50th anniversary, to take a closer look at the complexity and highlight some lesser-known general features of the clonal selection theory and of B cell activation that can be useful in formulating a quantitative version of this theory that includes class regulation and cellular heterogeneity.