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Discovery of the mechanism for V(D)J hypermutation remains a basic
goal of immunology despite the best efforts of many labo ratories.
The existence of catalyzed, site-specific mutation and its
exploitation for the somatic evolution of lymphocytes are re
markable adaptations, yet since the discovery of hypermutation in
1970 (see cover), much hard work has generated little. Indeed, our
knowledge of what is probably absolutely required for the mutator's
action can be succinctly expressed: /g gene enhancers. Table 1 of
Winter et a .'s chapter puts into a historical perspec tive how our
notions of the mutator have changed over the years. Despite these
modest gains, most of us feel that this is the best of times. Our
work has not only shown us what the mutator is not, it has also,
like an artist's preliminary sketch, defined the questions and
experiments we must face without diminishing the potential for new
biology. In short, it is great fun to toil against a significant
and enigmatic problem."
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