Decoding the molecular interplay of CD20 and therapeutic antibodies with fast volumetric nanoscopy

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2025-01-09 DOI:10.1126/science.adq4510

Arindam Ghosh, Mara Meub, Dominic A. Helmerich, Julia Weingart, Patrick Eiring, Thomas Nerreter, K. Martin Kortüm, Sören Doose, Markus Sauer

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Abstract

Elucidating the interaction between membrane proteins and antibodies requires whole-cell imaging at high spatiotemporal resolution. Lattice light-sheet (LLS) microscopy offers fast volumetric imaging but suffers from limited spatial resolution. DNA-based point accumulation for imaging in nanoscale topography (DNA-PAINT) achieves molecular resolution but is restricted to two-dimensional imaging owing to long acquisition times. We have developed two-dye imager (TDI) probes that enable ~15-fold faster imaging. Combining TDI-DNA-PAINT and LLS microscopy on immunological B cells revealed the oligomeric states and interaction of endogenous CD20 with the therapeutic monoclonal antibodies (mAbs) rituximab, ofatumumab, and obinutuzumab. Our results demonstrate that CD20 is abundantly expressed on microvilli that bind mAbs, which leads to an antibody concentration–dependent B cell polarization and stabilization of microvilli protrusions. These findings could aid rational design of improved immunotherapies targeting tumor-associated antigens.

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Science 综合性期刊-综合性期刊

CiteScore

61.10

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0.90%

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审稿时长

2.1 months

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