AID and somatic hypermutation

Robert W. Maul, Patricia J. Gearhart

Research output: Contribution to journalArticle

Abstract

In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation-induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation.

Original languageEnglish (US)
Pages (from-to)159-191
Number of pages33
JournalAdvances in Immunology
Volume105
Issue numberC
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

B-Lymphocytes
Antibody Diversity
Immunoglobulin Genes
Deoxyguanosine
Antibody Affinity
Uracil
Cytosine
DNA
DNA Replication
DNA Repair
Thymidine
Immunoglobulins
Genome
Mutation
AICDA (activation-induced cytidine deaminase)
Neoplasms
Proteins

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

AID and somatic hypermutation. / Maul, Robert W.; Gearhart, Patricia J.

In: Advances in Immunology, Vol. 105, No. C, 2010, p. 159-191.

Research output: Contribution to journalArticle

Maul, RW & Gearhart, PJ 2010, 'AID and somatic hypermutation', Advances in Immunology, vol. 105, no. C, pp. 159-191. https://doi.org/10.1016/S0065-2776(10)05006-6
Maul, Robert W. ; Gearhart, Patricia J. / AID and somatic hypermutation. In: Advances in Immunology. 2010 ; Vol. 105, No. C. pp. 159-191.
@article{ed22eceb7de04b5d8e33a0688a60e85b,
title = "AID and somatic hypermutation",
abstract = "In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation-induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation.",
author = "Maul, {Robert W.} and Gearhart, {Patricia J.}",
year = "2010",
doi = "10.1016/S0065-2776(10)05006-6",
language = "English (US)",
volume = "105",
pages = "159--191",
journal = "Advances in Immunology",
issn = "0065-2776",
publisher = "Academic Press Inc.",
number = "C",

}

TY - JOUR

T1 - AID and somatic hypermutation

AU - Maul, Robert W.

AU - Gearhart, Patricia J.

PY - 2010

Y1 - 2010

N2 - In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation-induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation.

AB - In response to an assault by foreign organisms, peripheral B cells can change their antibody affinity and isotype by somatically mutating their genomic DNA. The ability of a cell to modify its DNA is exceptional in light of the potential consequences of genetic alterations to cause human disease and cancer. Thus, as expected, this mechanism of antibody diversity is tightly regulated and coordinated through one protein, activation-induced deaminase (AID). AID produces diversity by converting cytosine to uracil within the immunoglobulin loci. The deoxyuracil residue is mutagenic when paired with deoxyguanosine, since it mimics thymidine during DNA replication. Additionally, B cells can manipulate the DNA repair pathways so that deoxyuracils are not faithfully repaired. Therefore, an intricate balance exists which is regulated at multiple stages to promote mutation of immunoglobulin genes, while retaining integrity of the rest of the genome. Here we discuss and summarize the current understanding of how AID functions to cause somatic hypermutation.

UR - http://www.scopus.com/inward/record.url?scp=77955964086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955964086&partnerID=8YFLogxK

U2 - 10.1016/S0065-2776(10)05006-6

DO - 10.1016/S0065-2776(10)05006-6

M3 - Article

C2 - 20510733

AN - SCOPUS:77955964086

VL - 105

SP - 159

EP - 191

JO - Advances in Immunology

JF - Advances in Immunology

SN - 0065-2776

IS - C

ER -