@article{4781,
  keywords = {Biomedical Engineering, Lymphoid tissues},
  author = {Zhe Zhong and Manuel Quiñones-Pérez and Zhonghao Dai and Valeria M. Juarez and Eshant Bhatia and Christopher R. Carlson and Shivem B. Shah and Anjali Patel and Zhou Fang and Thomas Hu and Mayar Allam and Sakeenah L. Hicks and Mansi Gupta and Sneh Lata Gupta and Ethan Weeks and Stephanie D. Vagelos and Alejandro Molina and Adriana Mulero-Russe and Ana Mora-Boza and Devyani J. Joshi and Rafick P. Sekaly and Todd Sulchek and Steven L. Goudy and Jens Wrammert and Krishnendu Roy and Jeremy M. Boss and Ahmet F. Coskun and Christopher D. Scharer and Andrés J. García and Jean L. Koff and Ankur Singh},
  title = {Human immune organoids to decode B cell response in healthy donors and patients with lymphoma},
  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.},
  year = {2024},
  journal = {Nature Materials},
  pages = {1-15},
  month = {2024-11-06},
  issn = {1476-4660},
  url = {https://www.nature.com/articles/s41563-024-02037-1},
  doi = {10.1038/s41563-024-02037-1},
  language = {en},
}