Affinity maturation of antibodies is characterized by localized hyperm
utation of the DNA around the V segment. Here we show, using mice cont
aining single or multiple transgene constructs, that an immunoglobulin
V-kappa segment can be replaced by human beta-globin or prokaryotic n
eo or gpt genes without affecting the rate of hypermutation; the V gen
e itself is not necessary for recruiting hypermutation. The ability to
target hypermutation to heterologous genes in vivo could find more ge
neral applications in biology.