title: Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor.
abstract: Integrating signals from multiple receptors allows cells to interpret the physiological context in which a signal is received. Here we describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signalling by another receptor. We show that the Toll-like receptor ligands lipopolysaccharide and CpG DNA, which are conserved microbial molecules, enhance signalling by the B-cell antigen receptor (BCR) by activating the actin-severing protein cofilin. Single-particle tracking reveals that increased severing of actin filaments reduces the spatial confinement of the BCR within the plasma membrane and increases BCR mobility. This allows more frequent collisions between BCRs and greater signalling in response to low densities of membrane-bound antigen. These findings implicate actin dynamics as a means of tuning receptor signalling and as a mechanism by which B cells distinguish inert antigens from those that are accompanied by indicators of microbial infection.
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Department of Cellular &Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [3] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [4] Program in Cell Biology, The Hospital for Sick Kids Research Institute, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.
authors: Spencer A
authors: SA
authors: Freeman
authors: Program in Cell Biology, The Hospital for Sick Kids Research Institute, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.
authors: Valentin
authors: V
authors: Jaumouillé
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Kate
authors: K
authors: Choi
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Brian E
authors: BE
authors: Hsu
authors: Program in Cell Biology, The Hospital for Sick Kids Research Institute, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.
authors: Harikesh S
authors: HS
authors: Wong
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [3] Department of Mathematics and Institute of Applied Mathematics, 1984 Mathematics Road, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z2.
authors: Libin
authors: L
authors: Abraham
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Department of Cellular &Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [3] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Marcia L
authors: ML
authors: Graves
authors: Department of Mathematics and Institute of Applied Mathematics, 1984 Mathematics Road, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z2.
authors: Daniel
authors: D
authors: Coombs
authors: 1] Department of Cellular &Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Calvin D
authors: CD
authors: Roskelley
authors: Department of Integrative Biology, University of Colorado Denver, 1151 Arapahoe, Denver, Colorado 80204, USA.
authors: Raibatak
authors: R
authors: Das
authors: Program in Cell Biology, The Hospital for Sick Kids Research Institute, 686 Bay Street, Toronto, Ontario, Canada M5G 0A4.
authors: Sergio
authors: S
authors: Grinstein
authors: 1] Department of Microbiology &Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3 [2] Life Sciences Institute I3 and Cell Research Groups, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.
authors: Michael R
authors: MR
authors: Gold
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015151:Immunoblotting; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000199:Actins; D008024:Ligands; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D051193:Toll-Like Receptors
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