Transfer of PBMC From SSc Patients Induces Autoantibodies and Systemic Inflammation in Rag2-/-/IL2rg-/- Mice

Frontiers in Immunology

Yaqing Shu¹  Junie D. Tchudjin Magatsin¹  Harald Heidecke¹  Antje Müller¹  Jacqueline Wax¹  Xiaoyang Yue¹  Gabriela Riemekasten¹  Frank Petersen²  Marjan Ahmadi³  Xinhua Yu⁴  Xiaoqing Wang⁴  Junping Yin⁴  Peter Lamprecht⁴  Brigitte Kasper⁴ 

[1] Allergy, Research Center Borstel, Airway Research Center North (ARCN), Members of the German Center for Lung Research (DZL), Borstel, Germany;Department of Histology and Embryology, School of Basic Medical Science, Guangxi Medical University, Guangxi, China;Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China;;Priority Area Asthma &

关键词: autoimmune diseases;    systemic sclerosis;    granulomatosis with polyangiitis;    peripheral blood mononuclear cells;    autoantibodies;    systemic inflammation;   

DOI  :  10.3389/fimmu.2021.677970

来源: DOAJ

【 摘 要 】

ObjectiveThe contribution of sustained autologous autoantibody production by B cells to the pathogenesis of systemic sclerosis (SSc) and granulomatosis with polyangiitis (GPA) is not fully understood. To investigate this, a humanized mouse model was generated by transferring patient-derived peripheral blood mononuclear cells (PBMC) into immunocompromised mice.MethodsPBMC derived from patients with SSc and GPA as well as healthy controls (HD) were isolated, characterized by flow cytometry, and infused into Rag2-/-/IL2rg-/- mice. In addition, PBMC from SSc patients treated with rituximab were transferred into mice. Twelve weeks later, human autoantibodies were determined in blood of the recipient mice and affected tissues were analyzed for pathological changes by histology and immunohistochemistry.ResultsMice engrafted with PBMC derived from SSc patients developed autoantibodies such as antinuclear antibodies (ANA) mimicking the pattern of the respective donors. Moreover, cellular infiltrates dominated by B cells were observed in lung, kidney and muscles of the recipient mice. By contrast, PBMC derived from HD or GPA patients survived in recipient mice after transfer, but neither human autoantibodies nor inflammatory infiltrates in tissues were detected. Furthermore, these pathological changes were absent in mice transferred with PBMC from rituximab-treated SSc patients.ConclusionThis humanized mouse model is indicative for cross-reactivity of human lymphocytes to murine autoantigens and argues for a pivotal role of B cells as well as of sustained autoimmunity in the pathogenesis of SSc. It provides a powerful tool to study interstitial lung disease and so far, under-recognized disease manifestations such as myositis and interstitial nephritis.

【 授权许可】

Unknown