| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; and
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Mayo Medical School, Rochester, MN 55905
Through their differential interactions with B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), the three BLyS family receptors play central roles in B cell survival and differentiation. Recent evidence indicates BLyS receptor levels shift following BCR ligation, suggesting that activation cues can alter overall BLyS receptor profiles and thus ligand sensitivity. In this study, we show that TLR stimuli also alter BLyS receptor expression, but in contrast to BCR ligation, TLR9 and TLR4 signals, preferentially increase transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) expression. Although both of these TLRs act through MyD88-dependent mechanisms to increase TACI expression, they differ in terms of their downstream mediators and the B cell subset affected. Surprisingly, only TLR4 relies on c-Rel and p50 to augment TACI expression, whereas TLR9 does not. Furthermore, although all follicular and marginal zone B cells up-regulate TACI in response to TLR9 stimulation, only marginal zone B cells and a subset of follicular B cells respond to TLR4. Finally, we find that both BLyS and APRIL enhance viability among quiescent and BCR-stimulated B cells. However, although BLyS enhances viability among TLR stimulated B cells, APRIL does not, suggesting that TACI but not BLyS receptor 3 may share survival promoting pathways with TLRs.
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 study is supported in part by Research Grants AI50213 and AI060729 (to W.N.K.) and Grant AI54488 (to M.P.C.) from the U.S. Public Health Service. K.L.H. and L.S.T. are supported by Training Grants AI069770 and RR07063, respectively, from the U.S. Public Health Service.
2 L.S.T. and G.C. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Michael P. Cancro, Department of Pathology and Laboratory Medicine, 284 John Morgan Building, University of Pennsylvania School of Medicine, 36th and Hamilton Walk, Philadelphia, PA 19104; E-mail address: cancro{at}mail.med.upenn.edu or Dr. Wasif N. Khan, Department of Microbiology and Immunology, Medical Center North A4207, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232; E-mail address: wasif.khan{at}vanderbilt.edu
4 Abbreviations used in this paper: BLyS, B lymphocyte stimulator; FO, follicular; MZ, marginal zone; TACI, transmembrane activator calcium modulator and cyclophilin ligand interactor; APRIL, a proliferation-inducing ligand; BCMA, B cell maturation Ag; TRIF, Toll/IL-1R domain-containing adaptor-inducing IFN-
.
This article has been cited by other articles:
|
|
 |
|
  A. Lartigue, N. Colliou, S. Calbo, A. Francois, S. Jacquot, C. Arnoult, F. Tron, D. Gilbert, and P. Musette Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus J. Immunol., November 15, 2009; 183(10): 6207 - 6216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Yuvaraj, G. Dijkstra, J. G. M. Burgerhof, P. M. Dammers, M. Stoel, A. Visser, F. G. M. Kroese, and N. A. Bos Evidence for Local Expansion of IgA Plasma Cell Precursors in Human Ileum J. Immunol., October 15, 2009; 183(8): 4871 - 4878. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Lee, I. Rauter, L. Garibyan, E. Ozcan, T. Sannikova, S. R. Dillon, A. C. Cruz, R. M. Siegel, R. Bram, H. Jabara, et al. The murine equivalent of the A181E TACI mutation associated with common variable immunodeficiency severely impairs B-cell function Blood, September 10, 2009; 114(11): 2254 - 2262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Crowley, J. E. Stadanlick, J. C. Cambier, and M. P. Cancro Fc{gamma}RIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation Blood, February 12, 2009; 113(7): 1464 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zekavat, S. Y. Rostami, A. Badkerhanian, R. F. Parsons, B. Koeberlein, M. Yu, C. D. Ward, T.-S. Migone, L. Yu, G. S. Eisenbarth, et al. In Vivo BLyS/BAFF Neutralization Ameliorates Islet-Directed Autoimmunity in Nonobese Diabetic Mice J. Immunol., December 1, 2008; 181(11): 8133 - 8144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Scholz, J. E. Crowley, M. M. Tomayko, N. Steinel, P. J. O'Neill, W. J. Quinn III, R. Goenka, J. P. Miller, Y. H. Cho, V. Long, et al. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact PNAS, October 7, 2008; 105(40): 15517 - 15522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hardenberg, L. Fernandez, J. Hendriks, K. Chebli, C. Jacquet, M. Sitbon, M. Hahne, and J. P. Medema APRIL facilitates viral-induced erythroleukemia but is dispensable for T cell immunity and lymphomagenesis J. Leukoc. Biol., August 1, 2008; 84(2): 380 - 388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kanswal, N. Katsenelson, A. Selvapandiyan, R. J. Bram, and M. Akkoyunlu Deficient TACI Expression on B Lymphocytes of Newborn Mice Leads to Defective Ig Secretion in Response to BAFF or APRIL J. Immunol., July 15, 2008; 181(2): 976 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xu, P. A. Santini, A. J. Matthews, A. Chiu, A. Plebani, B. He, K. Chen, and A. Cerutti Viral Double-Stranded RNA Triggers Ig Class Switching by Activating Upper Respiratory Mucosa B Cells through an Innate TLR3 Pathway Involving BAFF J. Immunol., July 1, 2008; 181(1): 276 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Cancro Different partners in different places? Blood, February 1, 2008; 111(3): 975 - 975. [Full Text] [PDF]
|
|
|
|
|
|
J. R. Darce, B. K. Arendt, X. Wu, and D. F. Jelinek Regulated Expression of BAFF-Binding Receptors during Human B Cell Differentiation J. Immunol., December 1, 2007; 179(11): 7276 - 7286. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
