2. Academic Validation
  3. Human immune organoids to decode B cell response in healthy donors and patients with lymphoma

Human immune organoids to decode B cell response in healthy donors and patients with lymphoma

  • Nat Mater. 2025 Feb;24(2):297-311. doi: 10.1038/s41563-024-02037-1.
Zhe Zhong 1 2 3,  Manuel Quiñones-Pérez 1 3,  Zhonghao Dai 1 3,  Valeria M Juarez 1 3,  Eshant Bhatia 1 3,  Christopher R Carlson 1 3,  Shivem B Shah 4,  Anjali Patel 3,  Zhou Fang 1 3,  Thomas Hu 1 3,  Mayar Allam 1 3,  Sakeenah L Hicks 5,  Mansi Gupta 5,  Sneh Lata Gupta 6,  Ethan Weeks 2,  Stephanie D Vagelos 7,  Alejandro Molina 8,  Adriana Mulero-Russe 1 9,  Ana Mora-Boza 1 2,  Devyani J Joshi 6,  Rafick P Sekaly 6,  Todd Sulchek 1 2,  Steven L Goudy 3 10,  Jens Wrammert 6,  Krishnendu Roy 11,  Jeremy M Boss 5 6,  Ahmet F Coskun 1 3,  Christopher D Scharer 5,  Andrés J García 1 2,  Jean L Koff 12,  Ankur Singh 13 14 15
Affiliations

Affiliations

  • 1 Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • 2 George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 3 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 4 Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • 5 Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • 6 Emory Vaccine Center, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • 7 School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • 8 School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
  • 9 School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • 10 Department of Otolaryngology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • 11 Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA.
  • 12 Winship Cancer Center, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • 13 Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA. ankur.singh@gatech.edu.
  • 14 George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. ankur.singh@gatech.edu.
  • 15 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. ankur.singh@gatech.edu.
PMID: 39506098 DOI: 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.

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