The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rahman, Z. S. M.
Right arrow Articles by Manser, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rahman, Z. S. M.
Right arrow Articles by Manser, T.
The Journal of Immunology, 2004, 173: 6179-6188.
Copyright © 2004 by The American Association of Immunologists

B Cells Expressing Bcl-2 and a Signaling-Impaired BAFF-Specific Receptor Fail to Mature and Are Deficient in the Formation of Lymphoid Follicles and Germinal Centers1

Ziaur S. M. Rahman and Tim Manser2

Department of Microbiology and Immunology and The Kimmel Cancer Institute, Thomas Jefferson Medical College, Philadelphia, PA 19017

The TNF family cytokine B cell-activating factor belonging to the TNF family (BAFF) (BLyS) plays a fundamental role in regulating peripheral B cell survival and homeostasis. A BAFF-specific receptor (BAFF-R; BR3) appears to mediate these functions via activation of the NF-{kappa}B2 pathway. Signaling by the BAFF-R is also required to sustain the germinal center (GC) reaction. Engagement of this receptor results in the induction of Bcl-2, suggesting that this antiapoptotic factor acts downstream of the BAFF-R and NF-{kappa}B2 pathway to promote peripheral B cell survival during primary and Ag-driven development. To test this idea, we created lines of mice coexpressing a Bcl-2 transgene and a signaling-deficient form of the BAFF-R derived from the B lymphopenic A/WySnJ strain. Surprisingly, although dramatically elevated numbers of B cells accumulate in the periphery of these mice, these B cells exhibit extremely perturbed primary development, formation of lymphoid microenvironments, and GC and IgG responses. Moreover, mice expressing the bcl-2 transgene alone display a loss of marginal zone B cells, an expansion of follicular B cells that appear immature, and alterations of the GC reaction. These results suggest that the BAFF-R and Bcl-2 regulate key and nonoverlapping aspects of peripheral B cell survival and development.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
S. M. Anderson, A. Khalil, M. Uduman, U. Hershberg, Y. Louzoun, A. M. Haberman, S. H. Kleinstein, and M. J. Shlomchik
Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity Cells
J. Immunol., December 1, 2009; 183(11): 7314 - 7325.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. L. Hoek, G. Carlesso, E. S. Clark, and W. N. Khan
Absence of Mature Peripheral B Cell Populations in Mice with Concomitant Defects in B Cell Receptor and BAFF-R Signaling
J. Immunol., November 1, 2009; 183(9): 5630 - 5643.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Vuyyuru, C. Mohan, T. Manser, and Z. S. M. Rahman
The Lupus Susceptibility Locus Sle1 Breaches Peripheral B Cell Tolerance at the Antibody-Forming Cell and Germinal Center Checkpoints
J. Immunol., November 1, 2009; 183(9): 5716 - 5727.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. T. Tamayo, L. C. Yoshimura, and R. J. Ford
BAFF-R promotes cell proliferation and survival through interaction with IKK{beta} and NF-{kappa}B/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells
Blood, May 7, 2009; 113(19): 4627 - 4636.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. Chattopadhyay, A. Q. Khan, G. Sen, J. Colino, W. duBois, A. Rubtsov, R. M. Torres, M. Potter, and C. M. Snapper
Transgenic Expression of Bcl-xL or Bcl-2 by Murine B Cells Enhances the In Vivo Antipolysaccharide, but Not Antiprotein, Response to Intact Streptococcus pneumoniae
J. Immunol., December 1, 2007; 179(11): 7523 - 7534.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. Neri, S. Kumar, M. T. Fulciniti, S. Vallet, S. Chhetri, S. Mukherjee, Y. Tai, D. Chauhan, P. Tassone, S. Venuta, et al.
Neutralizing B-Cell Activating Factor Antibody Improves Survival and Inhibits Osteoclastogenesis in a Severe Combined Immunodeficient Human Multiple Myeloma Model
Clin. Cancer Res., October 1, 2007; 13(19): 5903 - 5909.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Z. S. M. Rahman, B. Alabyev, and T. Manser
Fc{gamma}RIIB Regulates Autoreactive Primary Antibody-Forming Cell, but Not Germinal Center B Cell, Activity
J. Immunol., January 15, 2007; 178(2): 897 - 907.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. O. Jacob, L. Pricop, C. Putterman, M. N. Koss, Y. Liu, M. Kollaros, S. A. Bixler, C. M. Ambrose, M. L. Scott, and W. Stohl
Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF
J. Immunol., August 15, 2006; 177(4): 2671 - 2680.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. P. Miller, J. E. Stadanlick, and M. P. Cancro
Space, Selection, and Surveillance: Setting Boundaries with BLyS.
J. Immunol., June 1, 2006; 176(11): 6405 - 6410.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.