B cell receptor (BCR) cross-talk: IL-4 creates an alternate pathway for BCR-induced ERK activation that is phosphatidylinositol 3-kinase independent.
IL-4 has pleiotropic effects on B cells. These effects include alteration of subsequent BCR-triggered responses. To identify a molecular basis for this receptor cross-talk, we examined ERK activation and NF-kappaB induction. We found that treatment with IL-4, but not other cytokines, affected subsequent BCR signaling by creating a new pathway in which the need for PI3K in ERK activation was eliminated. In contrast, the need for PI3K in NF-kappaB induction was not altered. The new pathway for ERK required time to develop, depended on STAT6, and was blocked by inhibition of macromolecular synthesis. As in the classical pathway, BCR-induced ERK activation in the new, PI3K-independent pathway required MEK and was reflected in c-Raf. Thus, IL-4 promotes an alternate pathway through which BCR is coupled to Raf/MEK/ERK that may function to heighten the responsiveness of B cells during times of immunological stress.
Guo
Benchang
B
Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Rothstein
Thomas L
TL
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1