Abstract
T cell–independent type 1 agonists such as Gram-negative bacterial lipopolysaccharides can stimulate B lymphocytes to proliferate and produce antibodies by signaling through Toll-like receptors. This phenomenon is well established in vitro, yet polyclonal B cell responses after bacterial infection in vivo are often weak and short-lived. We show here that B cell proliferation and polyclonal antibody production in response to Gram-negative bacterial infection are modulated by acyloxyacyl hydrolase, a host enzyme that deacylates bacterial lipopolysaccharides. Deacylation of lipopolysaccharide occurred over several days, allowing lipopolysaccharide to act as an innate immune stimulant yet limiting the eventual amount of B cell proliferation and polyclonal antibody production. Control of lipopolysaccharide activation by acyloxyacyl hydrolase indicates that mammals can regulate immune responses to bacterial infection by chemical modification of a Toll-like receptor agonist.
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Acknowledgements
We thank R. Kitchens, R. Dziarski and L. Wetzler for advice. Supported by the National Institutes of Health (AI18188 and AI44642) and by the Jan and Henri Bromberg Chair in Internal Medicine (The University of Texas Southwestern Medical Center).
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Lu, M., Zhang, M., Takashima, A. et al. Lipopolysaccharide deacylation by an endogenous lipase controls innate antibody responses to Gram-negative bacteria. Nat Immunol 6, 989–994 (2005). https://doi.org/10.1038/ni1246
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DOI: https://doi.org/10.1038/ni1246
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