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Clinical and Vaccine Immunology, April 2008, p. 630-637, Vol. 15, No. 4
1071-412X/08/$08.00+0     doi:10.1128/CVI.00435-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Heather MacLeod,1,{dagger} Navneet Bhasin,2 and Lee M. Wetzler1,2*

Department of Microbiology, Immunology Training Program,1 Department of Medicine, Section of Infectious Diseases, Evans Biomedical Research Center, Boston University School of Medicine, Boston, Massachusetts 021182

Received 25 October 2007/ Returned for modification 14 December 2007/ Accepted 5 February 2008

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) I{kappa}B-{alpha} phosphorylation, leading to NF-{kappa}B nuclear translocation in B cells in a TLR2-dependent manner. PorB-induced NF-{kappa}B 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.

* Corresponding author. Mailing address: Section of Infectious Diseases, Boston University School of Medicine, 650 Albany St., EBRC Rm. 638, Boston, MA 02118. Phone: (617) 414-4394. Fax: (617) 414-5280. E-mail: lwetzler{at}bu.edu

{triangledown} Published ahead of print on 20 February 2008.

{dagger} Present address: Wyeth Inflammation, Wyeth Research, Cambridge, MA 02140.

Clinical and Vaccine Immunology, April 2008, p. 630-637, Vol. 15, No. 4
1071-412X/08/$08.00+0     doi:10.1128/CVI.00435-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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