Enhanced intra‐switch region recombination during immunoglobulin class switch recombination in 53BP1–/– B cells

Abstract

Immunoglobulin class switch recombination (CSR) is initiated by activation‐induced cytidine deaminase (AID), an enzyme that deaminates cytidine residues in single‐stranded DNA. U:G mismatches created by AID are processed to produce lesions that recruit and activate DNA damage response proteins including Ataxia‐telangiectasia mutated (ATM), histone H2AX, Nijmegen breakage syndrome 1 (Nbs1), and p53 binding protein 1 (53BP1). Among these proteins, absence of 53BP1 produces the most severe impairment of class switching. Here, we demonstrate that AID is targeted normally to switch region DNA and that intra‐switch region recombination is enhanced in 53BP1^–/– B cells. In addition, Sµ‐Sγ1 switch region junctions cloned from 53BP1^–/– B cells show unusual insertions suggestive of failed class switching. Our data are consistent with a role for 53BP1 in stabilizing the synapsis of switch regions during CSR.