Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop.
Type I IFNs play an important, yet poorly characterized, role in systemic lupus erythematosus. To better understand the interplay between type I IFNs and the activation of autoreactive B cells, we evaluated the effect of type I IFN receptor (IFNAR) deficiency in murine B cell responses to common TLR ligands. In comparison to wild-type B cells, TLR7-stimulated IFNAR(-/-) B cells proliferated significantly less well and did not up-regulate costimulatory molecules. By contrast, IFNAR1(-/-) B cells did not produce cytokines, but did proliferate and up-regulate activation markers in response to other TLR ligands. These defects were not due to a difference in the distribution of B cell populations or a failure to produce a soluble factor other than a type I IFN. Instead, the compromised response pattern reflected the disruption of an IFN-beta feedback loop and constitutively low expression of TLR7 in the IFNAR1(-/-) B cells. These results highlight subtle differences in the IFN dependence of TLR7 responses compared with other TLR-mediated B cell responses.
Green
Nathaniel M
NM
Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA.
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Kerstin
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Busconi
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Kim
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Brinkmann
Melanie M
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Trail
Erin Hodges
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Sean R
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Mark J
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Stefanie
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Connor
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Dan
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D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D025461:Feedback, Physiological / Q000276:immunology*; D016899:Interferon-beta / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
D016207:Cytokines; D008024:Ligands; D051199:Toll-Like Receptor 7; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta