Somatic hypermutation of VκJκ rearrangements: Targeting of RGYW motifs on both DNA strands and preferential selection of mutated codons within RGYW motifs

European Journal of Immunology

Volumn 29, Issue 12, 1999, Pages 4011-4021

  Foster, Sandra J ^b   Dörner, Thomas ^b   Lipsky, Peter E ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b NONE

Author keywords

Affinity maturation; Antibody; B lymphocyte; Generation of diversity; Somatic hypermutation

Indexed keywords

IMMUNOGLOBULIN J CHAIN; DNA; IMMUNOGLOBULIN HEAVY CHAIN; IMMUNOGLOBULIN KAPPA CHAIN;

ARTICLE; B LYMPHOCYTE; CODON; COMPLEMENTARITY DETERMINING REGION; DNA STRAND; GENE REARRANGEMENT; HUMAN; HUMAN CELL; IMMUNOGENETICS; IMMUNOGLOBULIN GENE; IMMUNOGLOBULIN VARIABLE REGION; NUCLEIC ACID BASE SUBSTITUTION; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SOMATIC MUTATION; GENETICS; IMMUNOLOGY; MUTATION;

B-LYMPHOCYTES; CODON; DNA; GENE REARRANGEMENT, B-LYMPHOCYTE; GENES, IMMUNOGLOBULIN; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN KAPPA-CHAINS; MUTATION;

EID: 0032585719     PISSN: 00142980     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-4141(199912)29:12<4011::AID-IMMU4011>3.0.CO;2-W     Document Type: Article

References (26)

1. Berek, C. and Milstein, C., The dynamic nature of the antibody repertoire. Immunol. Rev. 1988. 105: 5-26.
2. Neuberger, M. S. and Milstein, C., Somatic hypermutation. Curr. Opin. Immunol. 1995. 7: 248-254.
3. Jolly, C. J., Wagner, S. D., Rada, C., Klix, N., Milstein, C. and Neuberger, M. S., The targeting of somatic hypermutation. Semin. Immunol. 1996. 8: 159-168.
4. Reynaud, C. A., Garcia, C., Hein, W. R. and Weill, J. C., Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process. Cell 1995. 80: 115-125.
5. Reynaud, C. A., Quint, L., Bertocci, B. and Weill, J. C., What mechanism(s) drive hypermutation? Semin. Immunol. 1996. 8: 125-129.
6. Betz, A. G., Neuberger, M. S. and Milstein, C., Discriminating intrinsic and antigen-selected mutational hotspots in immunoglobulin V genes. Immunol. Today 1993. 14: 405-411.
7. Wagner, S. D., Milstein, C. and Neuberger, M. S., Codon bias targets mutation. Nature 1995. 376: 732.
8. Smith, D. S., Creadon, G., Jena, P. K., Portanova, J. P., Kotzin, B. L. and Wysocki, L. J., Di- and trinucleotide target preferences of somatic mutagenesis in normal and autoreactive B cells. J. Immunol. 1996. 156: 2642-2652.
9. H rearrangements. Immunol. Rev. 1998. 162: 161-171.
10. Foster, S. J., Dörner, T. and Lipsky, P. E., Targeting and subsequent selection of somatic hypermutations in the human Vx repertoire. Eur. J. Immunol. 1999. 10: 3122-3132.
11. Chang, B. and Casali, P., The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Immunol. Today 1994. 15: 367-372.
12. Golding, B. G., Gearhart, P. J. and Glickman, B. W., Patterns of somatic mutations in immunoglobulin variable genes. Genetics 1987. 115: 169-176.
13. Rogozin, I. B. and Kolchanov, N. A., Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighboring base sequences on mutagenesis. Biochim. Biophys. Acta 1992. 1171: 11-18.
14. Bachl, J. and Wabl, M., An immunoglobulin mutator that targets GC base pairs. Proc. Natl. Acad. Sci. USA 1996. 93: 851-855.
15. Dörner, T., Brezinschek, H.-P., Brezinschek, R. I., Foster, S. J., Domiati-Saad, R. and Lipsky, P. E., Analysis of the frequency and pattern of somatic mutations within nonproductively rearranged human variable heavy chain genes. J. Immunol. 1997. 158: 2779-2789.
16. Dörner, T., Foster, S. J., Farner, N. L. and Lipsky, P. E., Somatic hypermutation of human immunoglobulin heavy chain genes: targeting of RGYW motifs on both DNA strands. Eur. J. Immunol. 1998. 28: 3384-3396.
17. Maizels, N., Somatic hypermutation: How many mechanisms diversify V region sequences? Cell 1995. 83: 9-12.
18. Rogerson, B., Hackett, J., Peters, A., Haasch, D. Storb, U., Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication. EMBO J. 1991. 10: 4331-4341.
19. Storb, U., Peters, A., Klotz, E., Rogerson, B. and Hackett, J. Jr., The mechanism of somatic hypermutation studied with transgenic and transfected target genes. Semin. Immunol. 1996. 8: 131-140.
20. Milstein, C., Neuberger, M. S. and Staden, R., Both DNA strands of antibody genes are hypermutation targets. Proc. Natl. Acad. Sci. USA 1998. 95: 8791-8974.
21. Bachl, J., Steinberg, C. and Wabl, M., Critical test of hot spot motifs for immunoglobulin hypermutation. Eur. J. Immunol. 1997. 27: 3398-3403.
22. Shlomchik, M. J., Marshak-Rothstein, A., Wolfowicz, C. B., Rothstein, T. L. and Weigert, M. G., The role of clonal selection and somatic mutation in autoimmunity. Nature 1987. 328: 805-811.
23. Jukes, T. H. and King, J. L., Evolutionary nucleotide replacements in DNA. Nature 1997. 281: 605-606.
24. + B cells. J. Clin. Invest. 1997. 99: 1614-1627.
25. Farner, N., Dörner, T. and Lipsky, P. E., Molecular mechanisms and selection influence the generation of human VλJλ Repertoire. J. Immunol. 1999. 162: 2137-2145.
26. Kirkwood, B. R. (Ed.) Essentials of Medical Statistics. Blackwell Scientific Publications, Chicago, IL. 1988, pp. 57-64.