Aquaporin-5–specific heavy chain VDJ knock-in (A5H) mice reveal molecular mimicry–driven initiation and diversification of autoreactive B-cell responses
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By
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Hyunjin Kim
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Nayoon Lee
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Sabin Acharya
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Sungmin Kim
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Youngnim Choi
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July 2, 2026
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Objective:
To investigate how molecular mimicry shapes B-cell development and the evolution of antigen-specific B cell responses.
Approach:
- Model Development: Generated A5H mice, a knock-in model expressing a B-cell receptor binding to the AQP5 'E' epitope.
- B-cell Analysis: Examined B-cell development, anergy, and activation in response to microbial mimic peptides.
- Immunization Studies: Immunized A5H mice with PmE-L and assessed autoantibody production and germinal center responses.
Key Findings:
- A5H mice showed normal B-cell development with reduced anergy-associated B cells and an expanded pool of mimic-reactive B cells.
- At steady state, A5H mice produced anti-PmE-L antibodies, but not anti-AQP5E autoantibodies.
- Immunization with PmE-L led to robust production of anti-AQP5E autoantibodies that cross-reacted with AQP4 and AQP1.
- Heterozygous A5H mice exhibited stronger autoantibody responses compared to homozygous A5H mice.
Interpretation:
Limitations:
- Evidence of intramolecular epitope spreading to native AQP5 was not observed.
- Minimal tissue deposition of autoantibodies and salivary gland pathology.
Conclusion:
