| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology and Immunology, Dartmouth Medical School and The Norris Cotton Cancer Center, Lebanon, NH 03756;
Department of Autoimmunity and Inflammation, ZymoGenetics, Inc., Seattle, WA 98102;
Children’s Hospital Boston, Division of Immunology, Boston, MA 02115; and
Singapore Immunology Network Laboratory of Immune Regulation, Agency for Science, Technology, and Research, Singapore
Memory B (BMEM) cells and long-lived bone marrow plasma cells (BM-PCs) persist within local environmental survival niches that afford cellular longevity. However, the factors supporting BMEM cell survival within the secondary lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly characterized. We report herein that long-lived BMEM cell survival and function are completely independent of BAFF (B cell-activating factor of the TNF family) or APRIL (a proliferation-inducing ligand). Thus, BMEM cells represent the only mature B2 lineage subset whose survival is independent of these ligands. We have previously shown that the TNFR family member receptor BCMA (B cell maturation Ag) is a critical survival receptor for BM-PC survival in vivo. We identify in this study the ligands critical for BM-PC survival and show that either BAFF or APRIL supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL-dependent and -independent components of long-lived humoral immunity.
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 (NIH) Grants A1026296 and A108896 to R.J.N. and a NIH predoctoral training grant to M.J.B.
2 Address correspondence and reprint requests to Dr. Randolph J. Noelle, Norris Cotton Cancer Center, One Medical Center Drive, Rubin Building, Level 7, HB 7937, Lebanon, NH 03756. E-mail address: Randolph.Noelle{at}Dartmouth.edu
3 Abbreviations used in this paper: BMEM cell, memory B cell; APRIL, a proliferation inducing ligand; BAFF, B cell activating factor of the TNF family; BAFF-R, BAFF receptor; BCMA, B cell maturation Ag; BM, bone marrow; BM-PC, bone marrow plasma cell; GC, germinal center; het, heterozygous; KLH, keyhole limpet hemocyanin; mFc4, mutated Fc 4 region; NF, naive follicular (B cell); NP, (4-hydroxy-3-nitrophenyl)acetyl; PC, plasma cell; Spl-PC, splenic plasma cell; TACI, transmembrane activator and calcium modulator ligand interactor.
This article has been cited by other articles:
|
|
 |
|
  B. Zhao, A. Song, R. Haque, F. Lei, L. Weiler, X. Xiong, Y. Wu, M. Croft, and J. Song Cooperation between Molecular Targets of Costimulation in Promoting T Cell Persistence and Tumor Regression J. Immunol., June 1, 2009; 182(11): 6744 - 6752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Kimberley, L. van Bostelen, K. Cameron, G. Hardenberg, J. A. Marquart, M. Hahne, and J. P. Medema The proteoglycan (heparan sulfate proteoglycan) binding domain of APRIL serves as a platform for ligand multimerization and cross-linking FASEB J, May 1, 2009; 23(5): 1584 - 1595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Douagi, C. Gujer, C. Sundling, W. C. Adams, A. Smed-Sorensen, R. A. Seder, G. B. Karlsson Hedestam, and K. Lore Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells J. Immunol., February 15, 2009; 182(4): 1991 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Good, D. T. Avery, and S. G. Tangye Resting Human Memory B Cells Are Intrinsically Programmed for Enhanced Survival and Responsiveness to Diverse Stimuli Compared to Naive B Cells J. Immunol., January 15, 2009; 182(2): 890 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ponce Preclinical Support for Combination Therapy in the Treatment of Autoimmunity with Atacicept Toxicol Pathol, January 1, 2009; 37(1): 89 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Khuda, W. M. Loo, S. Janz, B. Van Ness, and L. D. Erickson Deregulation of c-Myc Confers Distinct Survival Requirements for Memory B Cells, Plasma Cells, and Their Progenitors J. Immunol., December 1, 2008; 181(11): 7537 - 7549. [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]
|
|
|
|
 |
|
 M. Carbonatto, P. Yu, M. Bertolino, E. Vigna, S. Steidler, L. Fava, C. Daghero, B. Roattino, M. Onidi, M. Ardizzone, et al. Nonclinical Safety, Pharmacokinetics, and Pharmacodynamics of Atacicept Toxicol. Sci., September 1, 2008; 105(1): 200 - 210. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
