title: B cells use mechanical energy to discriminate antigen affinities.
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.
authors.affiliation: Division of Immune Cell Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Natkanski
authors.forename: Wing-Yiu
authors.initials: WY
authors.lastname: Lee
authors.forename: Bhakti
authors.initials: B
authors.lastname: Mistry
authors.forename: Antonio
authors.initials: A
authors.lastname: Casal
authors.forename: Justin E
authors.initials: JE
authors.lastname: Molloy
authors.forename: Pavel
authors.initials: P
authors.lastname: Tolar
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D055595:Mechanical Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D024507:Nonmuscle Myosin Type IIA / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
chemical_list: D000941:Antigens; D011947:Receptors, Antigen, B-Cell; D024507:Nonmuscle Myosin Type IIA