| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology, Boston University School of Medicine, Boston, MA 02118;
Department of Medicine, Center for Lupus Research, University of Minnesota School of Medicine, Minneapolis, MN 55455;
Feinstein Institute for Medical Research, Manhasset, NY 11030;
Trudeau Institute, Saranac Lake, NY 12983; and
¶ Genentech, South San Francisco, CA 94080
We have previously shown that rheumatoid factors produced by Fas-deficient autoimmune-prone mice typically bind autologous IgG2a with remarkably low affinity. Nevertheless, B cells representative of this rheumatoid factor population proliferate vigorously in response to IgG2a/chromatin immune complexes through a mechanism dependent on the sequential engagement of the BCR and TLR9. To more precisely address the role of both receptors in this response, we analyzed the signaling pathways activated in AM14 B cells stimulated with these complexes. We found that the BCR not only serves to direct the chromatin complex to an internal compartment where it can engage TLR9 but also transmits a suboptimal signal that in combination with the signals emanating from TLR9 leads to NF-
B activation and proliferation. Importantly, engagement of both receptors leads to the up-regulation of a group of gene products, not induced by the BCR or TLR9 alone, that include IL-2. These data indicate that autoreactive B cells, stimulated by a combination of BCR and TLR9 ligands, acquire functional properties that may contribute to the activation of additional cells involved in the autoimmune disease process.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants AR-050256 (to A.M.-R.), AI-229690 (to T.L.R.), AI-50844 (to F.E.L.), and grants from the Alliance for Lupus Research (to T.W.B. and A.M.-R.).
2 Address correspondence and reprint requests to Dr. Ann Marshak-Rothstein, Department of Microbiology, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118. E-mail address: amrothst{at}bu.edu
3 Abbreviations used in this paper: IC, immune complex; ODN, oligodeoxynucleotide; PLC, phospholipase C; CsA, cyclosporin A; TNP, trinitrophenol.
This article has been cited by other articles:
|
|
 |
|
  A. M. Avalos, E. Latz, B. Mousseau, S. R. Christensen, M. J. Shlomchik, F. Lund, and A. Marshak-Rothstein Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B Oligonucleotides J. Immunol., November 15, 2009; 183(10): 6262 - 6268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Zhu, X. Liu, L. S. Treml, M. P. Cancro, and B. D. Freedman Mechanism and Regulatory Function of CpG Signaling via Scavenger Receptor B1 in Primary B Cells J. Biol. Chem., August 21, 2009; 284(34): 22878 - 22887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Green, A. Laws, K. Kiefer, L. Busconi, Y.-M. Kim, M. M. Brinkmann, E. H. Trail, K. Yasuda, S. R. Christensen, M. J. Shlomchik, et al. Murine B Cell Response to TLR7 Ligands Depends on an IFN-{beta} Feedback Loop J. Immunol., August 1, 2009; 183(3): 1569 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Eckl-Dorna and F. D. Batista BCR-mediated uptake of antigen linked to TLR9 ligand stimulates B-cell proliferation and antigen-specific plasma cell formation Blood, April 23, 2009; 113(17): 3969 - 3977. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
