B cell receptor cross-talk: exposure to lipopolysaccharide induces an alternate pathway for B cell receptor-induced ERK phosphorylation and NF-kappa B activation.
BCR signaling in naive B cells depends on the function of signalosome mediators; however, prior engagement of CD40 or of IL-4R produces an alternate signaling pathway in which Bruton's tyrosine kinase, PI3K, phospholipase Cgamma2, and protein kinase Cbeta are no longer required for BCR-induced downstream events. To explore the range of mediators capable of producing such an alternate pathway for BCR signaling, we examined the TLR4 agonist, LPS. B cell treatment with LPS at relatively low doses altered subsequent BCR signaling such that ERK phosphorylation and NF-kappaB activation occurred in a PI3K-independent manner. This effect of LPS extended to MEK phosphorylation and IkappaBalpha degradation, and it developed slowly over a period of 16-24 h. The involvement of TLRs is suggested by similar effects observed with a structurally distinct TLR agonist, PAM3CSK4 and by the need for MyD88 for induction of alternate BCR signaling by LPS. Thus, LPS-mediated TLR engagement produces an alternate pathway for BCR-triggered signal propagation that differs from the classical, signalosome-dependent pathway.
Dye
John R
JR
Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
Palvanov
Arkadiy
A
Guo
Benchang
B
Rothstein
Thomas L
TL
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020239:Receptor Cross-Talk / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013997:Time Factors
D002867:Chromones; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009025:Morpholines; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011947:Receptors, Antigen, B-Cell; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1