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Potential inhibition of somatic hypermutation by nucleoside analogues.
- Source :
-
Molecular immunology [Mol Immunol] 2007 Jan; Vol. 44 (4), pp. 666-9. Date of Electronic Publication: 2006 Apr 03. - Publication Year :
- 2007
-
Abstract
- Somatic hypermutation, which occurs in antigen-activated germinal centre B lymphocytes, diversifies the genes that encode immunoglobulin variable regions and leads to the 'affinity maturation' of the humoral immune response. Hypermutation affects dC/dG and dA/dT pairs with approximately equal frequency in vivo. DNA polymerase-theta contributes to hypermutagenesis at dC/dG pairs and DNA polymerase-eta is substantially involved in the generation of hypermutations at dA/dT pairs. The biochemical properties of polymerases-theta and -eta indicate that their DNA synthetic activities are potentially susceptible to inhibition by nucleoside analogues, so it is feasible that nucleoside analogues reduce the accumulation of dC/dG- and dA/dT-targeted hypermutations in vivo. Nucleoside analogues could hence impair the humoral adaptive immune response of HIV-infected patients who are prescribed these chemotherapeutic agents.
- Subjects :
- B-Lymphocytes immunology
DNA Replication immunology
DNA-Directed DNA Polymerase genetics
DNA-Directed DNA Polymerase immunology
HIV Infections genetics
HIV Infections immunology
HIV-1 genetics
HIV-1 immunology
Humans
Nucleosides immunology
Nucleosides pharmacology
DNA Polymerase theta
Nucleosides genetics
Somatic Hypermutation, Immunoglobulin drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0161-5890
- Volume :
- 44
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 16581133
- Full Text :
- https://doi.org/10.1016/j.molimm.2006.02.022