Role of protein tyrosine kinase and Erk1/2 activities in the Toll-like receptor 2-induced cellular activation of murine B cells by neisserial porin.
Neisserial porins are potent immune adjuvants and have been demonstrated to stimulate and induce the activation of human and murine B lymphocytes. Their immunopotentiating ability is due largely to the upregulation of the surface expression of the costimulatory ligand CD86 (B7-2) on B cells and other antigen-presenting cells. Porin-induced activation is dependent on the innate immune pattern recognition receptor Toll-like receptor 2 (TLR2). These data have led us to investigate the signal transduction events induced by PorB from Neisseria meningitidis and then, using inhibitors of these pathways, to establish the mechanism by which this bacterial major outer membrane protein induces CD86 upregulation and the proliferation of murine B cells. PorB was able to induce (i) protein tyrosine kinase (PTK) activity, (ii) the phosphorylation of Erk1 and Erk2, and (iii) IkappaB-alpha phosphorylation, leading to NF-kappaB nuclear translocation in B cells in a TLR2-dependent manner. PorB-induced NF-kappaB nuclear translocation was not dependent on either PTK or Erk1/2 activities. However, B-cell proliferation and the induction of increased surface expression of CD86 by PorB were dependent on PTK activity and not Erk1/2 activation. In conclusion, PorB acts through TLR2 as a B-cell mitogen, triggering tyrosine phosphorylation of various cellular proteins that are involved in proliferation and CD86 expression, as well as the phosphorylation of Erk1/2, which is not necessary for CD86 upregulation or the proliferation of B cells.
MacLeod
Heather
H
Department of Microbiology, Immunology Training Program, Evans Biomedical Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Bhasin
Navneet
N
Wetzler
Lee M
LM
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009345:Neisseria meningitidis / Q000276:immunology; D010766:Phosphorylation; D018272:Porins / Q000276:immunology* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation
D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D016328:NF-kappa B; D018272:Porins; D051195:Toll-Like Receptor 2; C057699:porin protein, Neisseria; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3