Ag. Betz et al., ELEMENTS REGULATING SOMATIC HYPERMUTATION OF AN IMMUNOGLOBULIN-KAPPA GENE - CRITICAL ROLE FOR THE INTRON ENHANCER MATRIX ATTACHMENT REGION, Cell, 77(2), 1994, pp. 239-248
Following encounter with antigen, the immunoglobulin genes in B lympho
cytes undergo somatic hypermutation. Most nucleotide substitutions are
introduced into a region flanked by the V gene promoter and intron en
hancer. Experiments described here using transgenic mice revealed that
the V kappa promoter does not contain specific signals since hypermut
ation was retained on substituting it by a beta-globin promoter. Howev
er, both the kappa intron and kappa 3' enhancer regions were found to
be essential for full hypermutation. This dependence of hypermutation
on both enhancers contrasts with transgene expression in hybridomas in
which only the 3' enhancer (and not the intron enhancer) is necessary
to achieve high mRNA levels. The results show that full hypermutation
depends on multiple elements, removal of some of which may drasticall
y impair but not totally abolish the process.