Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse
成果类型：
Article
署名作者：
McArthur, Hannah C. W.; Bajur, Anna T.; Iliopoulou, Maro; Spillane, Katelyn M.
署名单位：
University of London; King's College London; University of London; King's College London; Imperial College London
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-12459
DOI：
10.1073/pnas.2422528122
发表日期：
2025-05-20
关键词：
germinal center
ligand discrimination
subcapsular sinus
lateral mobility
receptor
memory
differentiation
proliferation
activation
mechanisms
摘要：
B cells discriminate antigens in immune synapses by capturing them from antigen-presenting cells (APCs). This discrimination relies on the application of mechanical force to B cell receptor (BCR)-antigen bonds, allowing B cells to selectively disrupt low-affinity interactions while internalizing high-affinity antigens. Using DNA-based tension sensors combined with high-resolution imaging, we demonstrate that the magnitude, location, and timing of forces within the immune synapse are influenced by the fluidity of the antigen-presenting membrane. Transitioning antigens from a high-mobility to a low-mobility substrate significantly increases the probability and speed of antigen extraction while also improving affinity discrimination. This shift in antigen mobility also reshapes the synapse architecture, altering spatial patterns of antigen uptake. Despite these adaptations, B cells maintain consistent levels of proximal and downstream signaling pathway activation regardless of antigen mobility. They also efficiently transport internalized antigens to major histocompatibility complex class II (MHCII)-positive compartments for processing. These results demonstrate that B cells mount effective responses to antigens across diverse physical environments, though the characteristics of that environment may influence the speed and accuracy of B cell adaptation during an immune response.