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Genetic Manipulation and Extended Culture of Human Germinal Center B Cells to Model Lymphomagenesis

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Specialty Molecular Biology
Date 2024 Oct 18
PMID 39424734
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Abstract

The germinal center (GC) is the stage of B cell differentiation that gives rise to a majority of B cell lymphomas. Here, we present an experimental coculture system for the ex vivo expansion and genetic manipulation of human GC B cells purified from discarded tonsil tissue. This system can be used to investigate the impact of defined genetic alterations, either individually or in combination, upon the growth and survival of human GC B cells in vitro. We provide examples of genetic combinations that lead to the immortalized growth of GC B cells in vitro, and others that result in malignant transformation in immunodeficient mice, allowing the creation of genetically bespoke, synthetic, human lymphoma models.

References
1.
Victora G, Nussenzweig M . Germinal Centers. Annu Rev Immunol. 2022; 40:413-442. DOI: 10.1146/annurev-immunol-120419-022408. View

2.
Pasqualucci L . Molecular pathogenesis of germinal center-derived B cell lymphomas. Immunol Rev. 2019; 288(1):240-261. DOI: 10.1111/imr.12745. View

3.
Shaffer 3rd A, Young R, Staudt L . Pathogenesis of human B cell lymphomas. Annu Rev Immunol. 2012; 30:565-610. PMC: 7478144. DOI: 10.1146/annurev-immunol-020711-075027. View

4.
Okosun J, Bodor C, Wang J, Araf S, Yang C, Pan C . Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2013; 46(2):176-181. PMC: 3907271. DOI: 10.1038/ng.2856. View

5.
Crouch S, Painter D, Barrans S, Roman E, Beer P, Cooke S . Molecular subclusters of follicular lymphoma: a report from the United Kingdom's Haematological Malignancy Research Network. Blood Adv. 2022; 6(21):5716-5731. PMC: 9619185. DOI: 10.1182/bloodadvances.2021005284. View