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논문 기본 정보

자료유형
학술저널
저자정보
Ahreum Lee (Seoul National University) Duck Kyun Yoo (Seoul National University College of Medicine) Yonghee Lee (Seoul National University) Sumin Jeon (Seoul National University) Suhan Jung (Seoul National University) Jinsung Noh (Seoul National University) Soyeon Ju (Seoul National University College of Medicine) Siwon Hwang (Seoul National University College of Medicine) Hong Hee Kim (Seoul National University) Sunghoon Kwon (Seoul National University) Junho Chung (Seoul National University College of Medicine) Youngnim Choi (Seoul National University)
저널정보
대한면역학회 Immune Network Immune Network Vol.21 No.5
발행연도
2021.10
수록면
34 - 49 (16page)

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Sjögren"s syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell “E” epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the “E” epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5Especific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

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ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES

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