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  • Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor.

Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor.

Nature communications (2015-02-04)
Spencer A Freeman, Valentin Jaumouillé, Kate Choi, Brian E Hsu, Harikesh S Wong, Libin Abraham, Marcia L Graves, Daniel Coombs, Calvin D Roskelley, Raibatak Das, Sergio Grinstein, Michael R Gold
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, purified by phenol extraction
Sigma-Aldrich
Lipopolysaccharides (rough strains) from Salmonella enterica serotype minnesota Re 595 (Re mutant)
Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, purified immunoglobulin, buffered aqueous solution