The evidence for somatic mutation a historical perspective

The relevant question then immediately became - does somatic mutation act only to diversify A chains This was particularly important to answer since there was now a body of evidence suggesting that a large number of different germ-line VK and VH genes were present in the mouse genome [73]. It was possible that sufficient diversity was germ-line encoded in these cases. 

At this point, several questions concerning somatic mutation remained Was mutation peculiar to myelomas or did it occur in normal B cells Were VH genes diversified by nucleotide replacement What fraction of the antibody diversity expressed by an animal is the result of somatic mutation and how much of this diversity is functional The pursuit of these questions awaited the development of hybridoma technology by Kohler and Milstein [84] and, thus, the ability to immortalize B cells that are participating in an immune response in vivo. 

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