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Updated: Apr 28, 2026

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AID and TET2 cooperate to demethylate Irf4 for plasma cell fate in germinal center B cells

Minghui He1, Roberta D'Aulerio1, Lia G Pinho1

  • 1Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

The Journal of Experimental Medicine
|April 27, 2026
PubMed

Activation-induced cytidine deaminase (AID) is essential for B cell affinity maturation. We investigated why AID deficiency gives rise to giant germinal centers (GCs) using the AIDR112H mouse model that is devoid of AID activity. The increased GC response was associated with accumulation of GC B cells in the light zone in immunized AIDR112H mice. AIDR112H GC B cells had reduced capacity to upregulate IRF4 to initiate plasma cell differentiation, leading to accumulation of a transitional GC population with reduced GL7 expression. Genetic introduction of a high-affinity B cell receptor was unable to restore plasma cell differentiation of AIDR112H B cells, while ectopic expression of catalytically active AID rescued plasma cell generation. AID and ten-eleven translocation 2 (TET2) synergistically facilitated demethylation of the Irf4 promoter/enhancer, and this was impeded in AIDR112H cells. These data reveal a B cell-intrinsic mechanism that governs the plasma cell fate decision through epigenetic remodeling mediated by AID in cooperation with TET2.

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