A hyper-IgM2 AID mutation limits IgH break formation but preserves affinity maturation.

Aicda R190X knock-in mice show a severe class switch recombination defect while preserving ongoing somatic hypermutation, with CSR linked to impaired switch-region double-strand break recombination.

• Why it matters: The human AID R190X mutation causes hyper-IgM syndrome with defective CSR but variable SHM, but how the AID C terminus separates these functions is unclear.
• What they did: The study created an Aicda R190X knock-in mouse and assessed CSR and SHM, then tested whether fusing AID R190X to catalytically inactive AID could rescue CSR.
• The result: CSR failure correlated with defective recombination of double-strand breaks in immunoglobulin switch regions, and catalytically inactive AID fusion restored CSR, implying a non-catalytic C-terminal role.

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