02650nas a2200529   4500000000100000000000100001008004100002260001500043653002700058653002100085100001400106700002800120700001700148700002200165700001800187700002700205700001900232700001700251700001400268700001400282700001600296700002200312700001600334700002000350700001600370700002500386700002100411700002500432700001800457700002100475700002100496700001700517700002000534700001800554700001900572700001900591700002000610700002700630700002300657700001700680700001600697245009800713856005500811300000900866520123100875022001402106       2024                            d  c2024-11-0610aBiomedical Engineering10aLymphoid tissues1 aZhe Zhong1 aManuel Quiñones-Pérez1 aZhonghao Dai1 aValeria M. Juarez1 aEshant Bhatia1 aChristopher R. Carlson1 aShivem B. Shah1 aAnjali Patel1 aZhou Fang1 aThomas Hu1 aMayar Allam1 aSakeenah L. Hicks1 aMansi Gupta1 aSneh Lata Gupta1 aEthan Weeks1 aStephanie D. Vagelos1 aAlejandro Molina1 aAdriana Mulero-Russe1 aAna Mora-Boza1 aDevyani J. Joshi1 aRafick P. Sekaly1 aTodd Sulchek1 aSteven L. Goudy1 aJens Wrammert1 aKrishnendu Roy1 aJeremy M. Boss1 aAhmet F. Coskun1 aChristopher D. Scharer1 aAndrés J. García1 aJean L. Koff1 aAnkur Singh00aHuman immune organoids to decode B cell response in healthy donors and patients with lymphoma  uhttps://www.nature.com/articles/s41563-024-02037-1  a1-153 aAntibodies 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.  a1476-4660