4.8 Article

B Cells Use Mechanical Energy to Discriminate Antigen Affinities

期刊

SCIENCE
卷 340, 期 6140, 页码 1587-1590

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1237572

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  1. Medical Research Council UK [U117597138, U117570592]
  2. Medical Research Council [MC_U117570592, MC_U117597138] Funding Source: researchfish
  3. MRC [MC_U117597138, MC_U117570592] Funding Source: UKRI

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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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