TY - JOUR
KW - Biomedical Engineering
KW - Lymphoid tissues
AU - Zhe Zhong
AU - Manuel Quiñones-Pérez
AU - Zhonghao Dai
AU - Valeria M. Juarez
AU - Eshant Bhatia
AU - Christopher R. Carlson
AU - Shivem B. Shah
AU - Anjali Patel
AU - Zhou Fang
AU - Thomas Hu
AU - Mayar Allam
AU - Sakeenah L. Hicks
AU - Mansi Gupta
AU - Sneh Lata Gupta
AU - Ethan Weeks
AU - Stephanie D. Vagelos
AU - Alejandro Molina
AU - Adriana Mulero-Russe
AU - Ana Mora-Boza
AU - Devyani J. Joshi
AU - Rafick P. Sekaly
AU - Todd Sulchek
AU - Steven L. Goudy
AU - Jens Wrammert
AU - Krishnendu Roy
AU - Jeremy M. Boss
AU - Ahmet F. Coskun
AU - Christopher D. Scharer
AU - Andrés J. García
AU - Jean L. Koff
AU - Ankur Singh
AB - 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.
BT - Nature Materials
DA - 2024-11-06
DO - 10.1038/s41563-024-02037-1
LA - en
N2 - 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.
PY - 2024
SP - 1
EP - 15
T2 - Nature Materials
TI - Human immune organoids to decode B cell response in healthy donors and patients with lymphoma
UR - https://www.nature.com/articles/s41563-024-02037-1
Y2 - 2024-12-02
SN - 1476-4660
ER -