Study Reveals Detailed Structure of B-Cell Receptor

Findings can inform vaccines, treatments for COVID, cancers, and beyond

microscope image of a ball-like cell with many protrusions
Receptors sprout from the surface of a human B cell in this colorized image taken with a scanning electron microscope. Image: NIAID

This article is part of Harvard Medical School’s continuing coverage of COVID-19.

Researchers at Harvard Medical School and the University of Freiberg in Germany have captured the first, long-awaited snapshots at near-atomic resolution of B-cell receptors — intricate assemblages of proteins protruding from the surface of B cells that detect invaders such as viruses and bacteria and alert the cells to fight.

The resulting three-dimensional structure, described Oct. 13 in Nature and based on imaging of mouse B-cell receptors, promises to deepen scientists’ understanding of how B cells function in health and disease. It also could advance efforts to thwart infections by pathogens such as SARS-CoV-2, improve vaccines, and develop new treatments for diseases that involve problems with B-cell receptors, such as some leukemias and lymphomas.

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Receptors allow B cells to perform their most critical roles: producing antibodies and remembering how to fight specific pathogens long after an initial infection. But how exactly receptors latch onto potential dangers and kick B cells into action has been one of the holes in the understanding of B-cell function.

Filling in those gaps requires revealing the tiniest details of what the receptors look like, both at rest and when they spring into action to attach to various molecules. It reflects a tenet of biology: structure illuminates function.

“Probing the structures of B-cell receptors provides clues about how a virus such as SARS-CoV-2 can be detected or escape detection,” said Ying Dong, research fellow in biological chemistry and molecular pharmacology in the lab of Hao Wu at HMS and Boston Children’s Hospital and co-first author of the study.

“That is one reason why revealing these structures is important in the context of the ongoing COVID-19 pandemic,” said Wu, professor of biological chemistry and molecular pharmacology in the Blavatnik Institute at HMS and the HMS Asa and Patricia Springer Professor of Structural Biology in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. Wu is co-senior author of the paper with Michael Reth at the University of Freiburg.