Accessibility control and machinery of immunoglobulin class switch recombination.

Abstract

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.