AID-Initiated Purposeful Mutations in Immunoglobulin Genes

Myron F. Goodman, Matthew D. Scharff, Floyd E. Romesberg

Research output: Chapter in Book/Report/Conference proceedingChapter

32 Scopus citations

Abstract

Exposure brings risk to all living organisms. Using a remarkably effective strategy, higher vertebrates mitigate risk by mounting a complex and sophisticated immune response to counter the potentially toxic invasion by a virtually limitless army of chemical and biological antagonists. Mutations are almost always deleterious, but in the case of antibody diversification there are mutations occurring at hugely elevated rates within the variable (V) and switch regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to and neutralizing foreign antigens throughout the body. These mutations are truly purposeful. This chapter is centered on activation-induced cytidine deaminase (AID). AID is required for initiating somatic hypermutation (SHM) in the V regions and class switch recombination (CSR) in the SR portions of Ig genes. By converting C → U, while transcription takes place, AID instigates a cascade of mutational events involving error-prone DNA polymerases, base excision and mismatch repair enzymes, and recombination pathways. Together, these processes culminate in highly mutated antibody genes and the B cells expressing antibodies that have achieved optimal antigenic binding undergo positive selection in germinal centers. We will discuss the biological role of AID in this complex process, primarily in terms of its biochemical properties in relation to SHM in vivo. The chapter also discusses recent advances in experimental methods to characterize antibody dynamics as a function of SHM to help elucidate the role that the AID-induced mutations play in tailoring molecular recognition. The emerging experimental techniques help to address long-standing conundrums concerning evolution-imposed constraints on antibody structure and function.

Original languageEnglish (US)
Title of host publicationAID for Immunoglobulin Diversity
EditorsFrederick Alt, Tasuku Honjo
Pages127-155
Number of pages29
DOIs
StatePublished - Jun 7 2007

Publication series

NameAdvances in Immunology
Volume94
ISSN (Print)0065-2776

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Goodman, M. F., Scharff, M. D., & Romesberg, F. E. (2007). AID-Initiated Purposeful Mutations in Immunoglobulin Genes. In F. Alt, & T. Honjo (Eds.), AID for Immunoglobulin Diversity (pp. 127-155). (Advances in Immunology; Vol. 94). https://doi.org/10.1016/S0065-2776(06)94005-X