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Cutting Edge |
* Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104; and
Human Genome Sciences, Inc., Rockville, MD 20850
These studies characterize BLyS responsiveness and receptor expression among transitional and mature peripheral B cells. The results show a maturation-associated increase in BLyS binding capacity that reflects differential expression patterns of the three BLyS receptors. Accordingly, BLyS administration enlarges only late transitional and mature peripheral B (MB) cell compartments. Furthermore, bromodeoxyuridine labeling and cell cycle analyses show these effects are mediated through enhanced proportional survival of cells traversing the T2, T3, and MB cell stages, rather than by causing proliferation or slowing transit within these subsets. Despite similar effects on survival, BLyS up-regulates the antiapoptotic genes A1and bcl-xL in MB cells but not immature B cells. Together, these findings show that, while BLyS influences B cell survival in several peripheral differentiation subsets, the downstream mediators differ, thus providing the first direct evidence for an established B lineage survival system whose intermediates change as B cells mature.
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J. Moreaux, E. Legouffe, E. Jourdan, P. Quittet, T. Reme, C. Lugagne, P. Moine, J.-F. Rossi, B. Klein, and K. Tarte BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone Blood, April 15, 2004; 103(8): 3148 - 3157. [Abstract] [Full Text] [PDF]
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M. Hikida, S. Johmura, A. Hashimoto, M. Takezaki, and T. Kurosaki Coupling Between B Cell Receptor and Phospholipase C-{gamma}2 Is Essential for Mature B Cell Development J. Exp. Med., August 18, 2003; 198(4): 581 - 589. [Abstract] [Full Text] [PDF]
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E. N. Hatada, R. K. G. Do, A. Orlofsky, H.-C. Liou, M. Prystowsky, I. C. M. MacLennan, J. Caamano, and S. Chen-Kiang NF-{kappa}B1 p50 Is Required for BLyS Attenuation of Apoptosis but Dispensable for Processing of NF-{kappa}B2 p100 to p52 in Quiescent Mature B Cells J. Immunol., July 15, 2003; 171(2): 761 - 768. [Abstract] [Full Text] [PDF]
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S. H. Smith and M. P. Cancro Cutting Edge: B Cell Receptor Signals Regulate BLyS Receptor Levels in Mature B Cells and Their Immediate Progenitors J. Immunol., June 15, 2003; 170(12): 5820 - 5823. [Abstract] [Full Text] [PDF]
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I. J. Amanna, J. P. Dingwall, and C. E. Hayes Enforced bcl-xL Gene Expression Restored Splenic B Lymphocyte Development in BAFF-R Mutant Mice J. Immunol., May 1, 2003; 170(9): 4593 - 4600. [Abstract] [Full Text] [PDF]
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V. Roschke, S. Sosnovtseva, C. D. Ward, J. S. Hong, R. Smith, V. Albert, W. Stohl, K. P. Baker, S. Ullrich, B. Nardelli, et al. BLyS and APRIL Form Biologically Active Heterotrimers That Are Expressed in Patients with Systemic Immune-Based Rheumatic Diseases J. Immunol., October 15, 2002; 169(8): 4314 - 4321. [Abstract] [Full Text] [PDF]
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