Abstract
In the course of T-cell dependent immune responses, antigen-activated B- lymphocytes migrate into B-cell follicles of secondary lymphoid organs and establish germinal centers (GC). In these structures, the proliferating GC B-cells activate the mechanism of somatic hypermutation, which introduces somatic mutations into rearranged immunoglobulin (Ig) V region genes [1, 2]. These mutations are (with rare exceptions) specific for Ig V genes and occur with a high rate of about 1 in 103–104 bp/cell cycle [1, 2]. In a selection process taking place within the GC, only GC B-cells which acquired favourable mutations, i. e. mutations that result in an increased affinity to the immunizing antigen, are allowed to survive and finally differentiate into either plasma cells or memory B-cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kocks C, Rajewsky K (1989) Stable expression and somatic hypermutation of antibody V regions in B-cell developmental pathways. Annu Rev Immunol 7:537–559
Rajewsky K (1996) Clonal selection and learning in the antibody system. Nature 381:751–758
Neuberger MS, Milstein C (1995) Somatic hypermutation. Curr Opin Immunol 7:248–254
Goossens T, Klein U, Küppers R (1998) Frequent occurrence of deletions and duplications during somatic hypermutation:Implications for oncogene translocations and heavy chain disease. Proc Natl Acad Sci USA 95:2463–2468
Fischer M, Küppers R (1998) Human IgA- and IgM-secreting intestinal plasma cells carry heavily mutated VH region genes. Eur J Immunol 28:2971–2977
Klein U, Rajewsky K, Küppers R (1998) Human immunoglobulin (Ig)M+IgD+ peripheral blood B-cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes:CD27 as a general marker for somatically mutated (memory) B-cells. J Exp Med 188:1679–1689
Wilson PC, de Bouteiller O, Liu Y-J, Potter K, Banchereau J, Capra J D, Pascual V (1998) Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes. J Exp Med 187:59–70
Ohlin M, Borrebaeck CAK (1998) Insertions and deletions in hypervariable loops of antibody heavy chains contribute to molecular diversity. Mol Immunol 35:233–238
Levy Y, Gupta N, Le Deist F, Garcia C, Fischer A, Weill J-C, Reynaud C-A (1998) Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome. Prot Natl Acad Sci USA 95:13135–13140
Klein U, Goossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K, Küppers R (1998) Somatic hypermutation in normal and transformed human B-cells. Immunol Rev 162:261–280
Kingzette M, Spieker-Polet H, Yam P-C, Zhai S-K, Knight KL (1998) Trans-chromosomal recombination within the Ig heavy chain switch region in B-lymphocytes. Prot Natl Acad Sci USA 95:11840–11845
Hiom K, Melek M, Gellert M (1998) DNA transposition by RAG1 and RAG2 proteins:a possible source of oncogenic translocations. Cell 94:463–470
Kato S, Tachibana K, Takayama N, Kataoka H, Yoshida MC, Takano T (1991) Genetic recombination in a chromosomal translocation t(2;8) (pi l;p24) of a Burkitt’s lymphoma cell line, KOBKIOI. Gene 97:239–244
Shen HM, Peters A, Baron B, Zhu X, Storb U (1998) Mutation of BCL-6 gene in normal B- cells by the process of somatic hypermutation of Ig genes. Science 280:1750–1752
Pasqualucci L, Migliazza A, Fracchiolla N, William C, Neri A, Baldini L, Changanti RSK, Klein U, Küppers R, Rajewsky K, Dalla-Favera R (1998) BCL-6 mutations in normal germinal center B-cells:Evidence of somatic hypermutation acting outside Ig loci. Prot Natl Acad Sci USA 95:11816–11821
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer-Verlag
About this paper
Cite this paper
Küppers, R., Goossens, T., Klein, U. (1999). The Role of Somatic Hypermutation in the Generation of Deletions and Duplications in Human Ig V Region Genes and Chromosomal Translocations. In: Melchers, F., Potter, M. (eds) Mechanisms of B Cell Neoplasia 1998. Current Topics in Microbiology and Immunology, vol 246. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60162-0_24
Download citation
DOI: https://doi.org/10.1007/978-3-642-60162-0_24
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64283-8
Online ISBN: 978-3-642-60162-0
eBook Packages: Springer Book Archive