ANALYSIS OF SOMATIC HYPERMUTATION IN MOUSE PEYER PATCHES USING IMMUNOGLOBULIN-KAPPA LIGHT-CHAIN TRANSGENES

被引:91
作者
GONZALEZFERNANDEZ, A
MILSTEIN, C
机构
[1] Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, Hills Road
关键词
ANTIBODY TRANSGENES; GERMINAL CENTERS; MUTATION HOTSPOTS; GENE CONVERSION;
D O I
10.1073/pnas.90.21.9862
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have exploited mice transgenic for an immunoglobulin kappa light chain in order to show thal immunoglobulin genes in the B cells of Peyer's patches in unimmunized mice carry a high level of somatic mutations. Most of the mutations are found in the subpopulation of B cells which, based on peanut agglutinin binding, derive from the germinal centers. The number of mutations per clone and their distribution along the variable gene segment (indicative of untemplated point mutations) are very similar to those found in antigen-specific splenic B cells of normal mice after secondary immunization. The mutations accumulate mainly in complementarity-determining region 1, in particular in some specific codons (Ser-26, Ser-31, and Ser-77) which have been previously recognized as intrinsic hypermutational hotspots. These results suggest that, as in the spleen, somatic mutation occurs in B cells which have migrated to the germinal centers, probably as a consequence of stimulation by antigens present in the gut environment. Transgenic animals are increasingly being used to define the signals involved in hypermutation. However, their subsequent study is very time-consuming because it is based on immunization and analysis of hybridomas or antigen-selected cells. We propose that the use of Peyer's patches of unimmunized adult mice offers a reliable and simple approach to analyze hypermutation of transgenes.
引用
收藏
页码:9862 / 9866
页数:5
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