Cutting Edge: ATM Influences Germinal Center Integrity

J Immunol. 2019 Jun 1;202(11):3137-3142. doi: 10.4049/jimmunol.1801033. Epub 2019 Apr 26.


The DNA damage response protein ATM has long been known to influence class switch recombination in ex vivo-cultured B cells. However, an assessment of B cell-intrinsic requirement of ATM in humoral responses in vivo was confounded by the fact that its germline deletion affects T cell function, and B:T cell interactions are critical for in vivo immune responses. In this study, we demonstrate that B cell-specific deletion of ATM in mice leads to reduction in germinal center (GC) frequency and size in response to immunization. We find that loss of ATM induces apoptosis of GC B cells, likely due to unresolved DNA lesions in cells attempting to undergo class-switch recombination. Accordingly, suboptimal GC responses in ATM-deficient animals are characterized by decreased titers of class-switched Abs and decreased rates of somatic hypermutation. These results unmask the critical B cell-intrinsic role of ATM in maintaining an optimal GC response following immunization.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • B-Lymphocytes / physiology*
  • Cells, Cultured
  • DNA Repair / genetics
  • Germinal Center / physiology*
  • Immunoglobulin Class Switching
  • Mice
  • Mice, Knockout
  • Receptors, Complement 3d / genetics
  • Somatic Hypermutation, Immunoglobulin
  • T-Lymphocytes / physiology*


  • Receptors, Complement 3d
  • Ataxia Telangiectasia Mutated Proteins