International Immunology, Vol. 13, No. 11, 1415-1422,
November 2001
© 2001 Japanese Society for Immunology
The PU.1 and NF-EM5 binding motifs in the Ig
3' enhancer are responsible for directing somatic hypermutations to the intrinsic hotspots in the transgenic V gene
Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
1 Department of Immunology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
Correspondence to: H. Sakano
Somatic hypermutation is a key mechanism in generating Ig with higher affinities to antigen, a process known as affinity maturation. Using Ig
transgenes, the 3' enhancer (E3') has been shown to play an important role in introducing hypermutations. In order to identify the cis-acting elements that regulate hypermutagenesis, we have generated transgenic substrates containing mutations/deletions in the E3' region. Here, we report that base substitutions in the E3', either in the PU.1 or in the NF-EM5 binding motif, not only reduce the mutation rate but also disrupt the directed mutagenesis in the intrinsic hotspots of the Ig transgene.
Keywords: antibodies, B lymphocytes, generation of diversity, transgenic, knock-out
Transmitting editor: T. Taniguchi
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