ArticleProceedings of the National Academy of Sciences of the United States of America1995
Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- T-bet regulates IgG class switching and pathogenic autoantibody production.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Advances in animal cell recombinant protein production: GS-NS0 expression system.Cytotechnology · 2000Article
- Human B cells accumulate immunoglobulin V gene somatic mutations in a cell contact-dependent manner in cultures supported by activated T cells but not in cultures supported by CD40 ligand.Clinical and experimental immunology · 1999Article
- Induction of Ig somatic hypermutation and class switching in a human monoclonal IgM+ IgD+ B cell line in vitro: definition of the requirements and modalities of hypermutation.Journal of immunology (Baltimore, Md. : 1950) · 1999Article
- A role for RAD51 in the generation of immunoglobulin gene diversity in rabbits.Journal of immunology (Baltimore, Md. : 1950) · 1999Article
- The Ig mutator is dependent on the presence, position, and orientation of the large intron enhancer.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Sequence dependent hypermutation of the immunoglobulin heavy chain in cultured B cells.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- The promotion of V region hypermutation.The Journal of experimental medicine · 1997Article
- Differential V region mutation of two transfected Ig genes and their interaction in cultured B cell lines.The EMBO journal · 1996Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Somatic mutation of the variable (V) regions of immunoglobulin genes occurs in vivo at rates that have been estimated to be between 10(-3) and 10(-4) per bp per generation. To study this process in vitro, the 18.81 pre-B-cell line and hybrids derived by fusing 18.81 to the NSO myeloma fusion partner were transfected with a mu heavy-chain construct containing a nonsense mutation in the V region (Vn) or the constant region (Cn). Mutation was quantitated by reversion analysis using the ELISA spot assay to detect single cells secreting IgM. Fluctuation analysis revealed that V-region mutations spontaneously occurred in 18.81 cells at an average rate of 5.8 x 10(-6) per bp per cell generation and in selected 18.81-NSO hybrids at greatly increased rates of 1.6 x 10(-3) to 5.8 x 10(-4) per bp per generation. The Vn construct also reverted frequently in transgenic mice, indicating that it contained sufficient information to mutate at high rates both in vivo and in vitro. Sequence analysis of reverted genes revealed that reversion was due to point mutations. Since the rates and nature of the mutations that are occurring in these transfected genes are similar to those reported in vivo, it should be possible to use this system to identify the cis-acting sequences and trans-acting factors that are responsible for V-region somatic hypermutation.
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