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1
*
Department of Immunology, The Scripps Research Institute, La Jolla, CA, 92037;
Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201
To examine a role of DNA polymerase 
in somatic hypermutation,
we generated transgenic mice that express antisense RNA to a portion of
mouse REV3, the gene encoding this polymerase. These
mice express high levels of antisense RNA, significantly reducing the
levels of endogenous mouse REV3 transcript.
Following immunization to a hapten-protein complex, transgenic mice
mounted vigorous Ab responses, accomplished the switch to IgG, and
formed numerous germinal centers. However, in most transgenic animals,
the generation of high affinity Abs was delayed. In addition,
accumulation of somatic mutations in the VH genes of memory
B cells from transgenic mice was decreased, particularly among those
that generate amino acid replacements that enhance affinity of the B
cell receptor to the hapten. These data implicate DNA polymerase , a
nonreplicative polymerase, in the process of affinity maturation,
possibly through a role in somatic hypermutation, clonal selection, or
both.
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