B cell receptor cross-talk: exposure to lipopolysaccharide induces an alternate pathway for B cell receptor-induced ERK phosphorylation and NF-kappa B activation
Dye, J.R.; Palvanov, A.; Guo, B.; Rothstein, T.L.
Journal of Immunology 179(1): 229-235
2007
ISSN/ISBN: 0022-1767 PMID: 17579042 Document Number: 608588
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, P13K, phospholipase C gamma 2, and protein kinase C,6 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-kappa B activation occurred in a P13K-independent manner. This effect of LPS extended to MEK phosphorylation and I kappa B alpha 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.