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(Journal of Leukocyte Biology. 2003;73:323-332.)
© 2003 by Society for Leukocyte Biology

Accessibility control and machinery of immunoglobulin class switch recombination

Ke Zhang

The Hart and Louse Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, University of California Los Angeles, School of Medicine

Correspondence: Ke Zhang, 52-175, CHS Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1680. E-mail: kzhang{at}mednet.ucla.edu

Immunoglobulin (Ig) class switching is a process by which B lymphocytes shift from production of IgM to other Ig classes and subclasses via Ig class switch recombination (CSR). Multiple cellular and molecular processes are involved in CSR. Induction of a given IgH germline transcription initiates CSR processes. Ig germline transcription is selectively activated and induced by specific cytokine(s) via cytokine-specific signal pathways, synergized by CD40 signaling, and optimized by the 3' Ig{alpha} enhancers through locus control region function. Following Ig germline transcription, the switch-region DNA undergoes conformational changes so that it can serve as an appropriate substrate for nicking and cleavage by switch recombination machinery. Finally, the double-strand breaks in donor and acceptor switch DNAs are processed, repaired, and ligated through a general nonhomologous end join pathway. CSR generates a new transcriptional unit for production of a class-switched Ig isotype.

Key Words: germline transcription • 3' Ig{alpha} enhancer • DNA repair




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