2024-11-12 ジョージア工科大学
<関連情報>
- https://research.gatech.edu/lab-grown-human-immune-system-model-uncovers-weakened-response-cancer-patients
- https://www.nature.com/articles/s41563-024-02037-1
ヒト免疫オルガノイドが健康なドナーとリンパ腫患者のB細胞応答を解読する Human immune organoids to decode B cell response in healthy donors and patients with lymphoma
Zhe Zhong,Manuel Quiñones-Pérez,Zhonghao Dai,Valeria M. Juarez,Eshant Bhatia,Christopher R. Carlson,Shivem B. Shah,Anjali Patel,Zhou Fang,Thomas Hu,Mayar Allam,Sakeenah L. Hicks,Mansi Gupta,Sneh Lata Gupta,Ethan Weeks,Stephanie D. Vagelos,Alejandro Molina,Adriana Mulero-Russe,Ana Mora-Boza,Devyani J. Joshi,Rafick P. Sekaly,Todd Sulchek,Steven L. Goudy,Jens Wrammert,… Ankur Singh
Nature Materials Published:06 November 2024
DOI:https://doi.org/10.1038/s41563-024-02037-1
Abstract
Antibodies are produced when naive B cells differentiate into plasma cells within germinal centres (GCs) of lymphoid tissues. Patients with B cell lymphoma on effective immunotherapies exhibit diminished antibody production, leading to higher infection rates and reduced vaccine efficacy, even after B cell recovery. Current ex vivo models fail to sustain long-term GC reactions and effectively test B cell responses. Here we developed synthetic hydrogels mimicking the lymphoid tissue microenvironment, enabling human GCs from tonsils and peripheral blood mononuclear cell-derived B cells. Immune organoids derived from peripheral blood mononuclear cells maintain GC B cells and plasma cells longer than tonsil-derived ones and exhibit unique B cell programming, including GC compartments, somatic hypermutation, immunoglobulin class switching and B cell clones. Chemical inhibition of transcriptional and epigenetic processes enhances plasma cell formation. While integrating polarized CXCL12 protein in a lymphoid organ-on-chip modulates GC responses in healthy donor B cells, it fails with B cells derived from patients with lymphoma. Our system allows rapid, controlled modelling of immune responses and B cell disorders.
