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  Cornell University

MAE Publications and Papers

Sibley School of Mechanical and Aerospace Engineering

New article: Modular Immune Organoids with Integrin Ligand Specificity Differentially Regulate Ex Vivo B Cell Activation

Article:  Purwada, A; Shah, SB; Beguelin, W; Melnick, AM; Singh, A; “Modular Immune Organoids with Integrin Ligand Specificity Differentially Regulate Ex Vivo B Cell Activation”, ACS Biomaterials Science & Engineering, 3 (2): 214-225

DOI

Abstract: Germinal centers are dynamic structures within lymphoid tissues, which develop once B cells receive activating signals from surrounding immune cells. Germinal center B cells are small in number, heterogeneous, and prone to rapid apoptosis unless selected by the body to form memory B cells. Despite extensive research in the B cell differentiation process, the role of the lymphoid niche, in particular integrin ligands, in the development of early germinal center-like phenotype remains unclear.

Here, we report a biomaterials-based modular immune organoid that enables development of early germinal center phenotype in an integrin ligand-specific manner. We demonstrate the differential role of integrin alpha 4 beta 1- and alpha v beta 3-binding ligands in the induction of GL7+ (GC-like) and GL7- (non-GC-like) phenotype in differentiating Bcells while in the presence of CD40 ligand and interleukin-4. We further demonstrate the role of integrin ligand specificities in clustering of beta 3 integrin and B cell receptor on the surface of differentiated B cells in 3D organoids as compared to the classic 2D cocultures. The study demonstrates that biomaterials-based immune organoids represent an ex vivo platform technology, which recapitulates certain aspects of GC biology to understand the process of B cell differentiation and induction of immunological responses. This platform is particularly useful in understanding the role of selective biomolecular signals and the temporal dependency of immune responses to these signals.

Funding Acknowledgement:  National Science Foundation CAREER award [DMR-1554275]; Cornell University’s Presidential Life Sciences Fellowship

Funding Text:  We acknowledge financial support from the National Science Foundation CAREER award (DMR-1554275 (AS.)). We also acknowledge academic scholarship support from Cornell University’s Presidential Life Sciences Fellowship (S.B.S.). We acknowledge the Cornell University Biotechnology Resource Center (BRC) Imaging Facility and NIH 1S10RR025502 for data collected on the Zeiss LSM 710 Confocal.

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