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Updated: May 22, 2026
09:49
Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
Published on: August 13, 2010
Origin of immunoglobulin isotype switching
Catherine Zhu1, Victor Lee, Alyssa Finn
1Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.
Current Biology : CB
|May 1, 2012
Summary
Shark immunoglobulin class switching occurs through DNA recombination between distant genes, even across chromosomes. This process, initiated by activation-induced cytidine deaminase (AID), reveals an ancient mechanism for antibody diversity in jawed vertebrates.
Area of Science:
- Immunology
- Evolutionary Biology
- Genetics
Background:
- Immunoglobulin class switching diversifies antibody effector functions via DNA recombination.
- Sharks possess a unique immunoglobulin gene organization with numerous autonomous miniloci.
- This gene organization represents an early stage in jawed vertebrate evolution.
Purpose of the Study:
- To investigate the mechanism of immunoglobulin class switching in sharks.
- To understand the role of gene organization in antibody diversification.
- To explore the evolutionary origins of class switch recombination.
Main Methods:
- Analysis of V(D)J rearrangement and gene expression in shark immunoglobulin loci.
- Investigation of DNA recombination events, including reciprocal exchanges and transchromosomal recombination.
- Examination of somatic hypermutation activity and switch site characteristics.
Main Results:
- VDJ can be expressed with constant regions from spatially distant clusters (>120 kb).
- Reciprocal exchanges occur between Igω and Igμ genes, augmented by immunization.
- Switching involves transchromosomal recombination and occurs independently of linkage position.
Conclusions:
- Shark class switching is mediated by cutting/joining of distal DNA lesions, likely initiated by activation-induced cytidine deaminase (AID).
- This process occurs in the absence of mammalian-type switch regions.
- Autonomous IgH loci in sharks, prone to programmed DNA breakage, may have facilitated the evolution of class switch recombination.
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