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B Cells Use Mechanical Energy to Discriminate Antigen Affinities

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Science  28 Jun 2013:
Vol. 340, Issue 6140, pp. 1587-1590
DOI: 10.1126/science.1237572

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B Cell Tug of War

High-affinity, protective antibodies made by B cells are critical for providing long-term protection against reinfection. In order to produce antibodies, B cells must first bind to and extract antigens from the surface of antigen-presenting cells. Using an in vitro system that allows B cells to bind to antigenladen, flexible membranes, Natkanski et al. (p. 1587, published online 16 May) show that antigen extraction relies on myosin IIA–mediated contractile forces that pull upon the antigen-presenting membrane. These forces break the antigen-receptor bonds if affinity is low, thus ensuring that B cells only extract, internalize, and presumably respond to, high-affinity antigens.

Abstract

The generation of high-affinity antibodies depends on the ability of B cells to extract antigens from the surfaces of antigen-presenting cells. B cells that express high-affinity B cell receptors (BCRs) acquire more antigen and obtain better T cell help. However, the mechanisms by which B cells extract antigen remain unclear. Using fluid and flexible membrane substrates to mimic antigen-presenting cells, we showed that B cells acquire antigen by dynamic myosin IIa–mediated contractions that pull out and invaginate the presenting membranes. The forces generated by myosin IIa contractions ruptured most individual BCR-antigen bonds and promoted internalization of only high-affinity, multivalent BCR microclusters. Thus, B cell contractility contributes to affinity discrimination by mechanically testing the strength of antigen binding.

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