期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：10
页码：7003-7008
DOI：10.1073/pnas.092160999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Somatic hypermutation generates variants of antibody genes and underpins the affinity maturation of antibodies. It is restricted to the V-gene segments, and although it decays exponentially toward the 3'end, it includes recognizable hot spots. Although the detailed mechanism of hypermutation remains elusive, the process may take place in two separate stages, preferentially targeting G/Cs in the first and A/Ts in the second stage. It seems that MSH2 is involved in the second stage, and that activation induced deaminase (AID) is implicated in the control of hypermutation. The constitutively hypermutating cell line Ramos expresses AID, and we have prepared transfectants that express a chimeric AID-green fluorescent protein. The fluorescence is strongly detected in the cytoplasm but not in the nucleus. Yet, the chimeric protein increases the hypermutation rate either directly or, more likely, indirectly, by favoring the transport of AID into the nucleus. Thus, in Ramos, AID seems to be rate limiting. Unexpectedly, the proportion of deletions also is increased. The increase in mutation rate detected by a fast cytofluorimetric method based on the accumulation of sIgM-loss mutants correlates with the increase measured by mutations defined by sequence analysis. The higher mutation rate is largely explained by the higher proportion of mutated clones, indicating that AID controls the number of cells that undergo hypermutation but not the number of mutations that are incorporated in each mutation round.
