| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143;
Institute of Immunology, Hannover Medical School, Hannover, Germany; and
Molecular Tumorgenetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
Results from several mouse tolerance models indicate that autoreactive B cells in peripheral lymphoid organs develop an anergic phenotype, migrate to the boundary between the T cell zone and the B cell follicle (T/B boundary), and undergo rapid cell death. We have used B cells from mice that are double-transgenic for soluble hen egg lysozyme (HEL) and an Ig that recognizes HEL with a high affinity to characterize the mechanisms underlying the migration and elimination of autoreactive B cells. In contrast to the situation for acutely activated B cells, we find that anergic B cells have reduced levels of CXCR5, the receptor for the follicular chemokine, CXCL13, and this contributes to their exclusion from follicles. CCR7 expression is required for follicular exclusion of anergic cells, although up-regulation of the receptor does not appear to be necessary. By TUNEL analysis, we observe that excluded anergic cells die in situ at the T/B boundary. We also show that this elimination occurs via a Fas-independent mechanism. Using CCR7−/−IgHEL-transgenic B cells we find that localization to the T/B boundary is not a necessary event to achieve the competitive elimination of autoantigen-binding B cells. These findings characterize the mechanism for follicular exclusion of autoantigen-binding B cells and they indicate that B cells compete for survival by mechanisms that are separate from competition for the follicular niche.
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, S. C. Su, D. B. Hecox, G. F. Brady, K. M. Mackin, A. G. Clark, and M. H. Foster Central Tolerance Regulates B Cells Reactive with Goodpasture Antigen {alpha}3(IV)NC1 Collagen J. Immunol., November 1, 2008; 181(9): 6092 - 6100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Witsch and E. Bettelheim Allelic and Isotypic Light Chain Inclusion in Peripheral B Cells from Anti-DNA Antibody Transgenic C57BL/6 and BALB/c Mice J. Immunol., March 15, 2008; 180(6): 3708 - 3718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Haynes, C. D. C. Allen, R. Lesley, K. M. Ansel, N. Killeen, and J. G. Cyster Role of CXCR5 and CCR7 in Follicular Th Cell Positioning and Appearance of a Programmed Cell Death Gene-1High Germinal Center-Associated Subpopulation J. Immunol., October 15, 2007; 179(8): 5099 - 5108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Horikawa, S. W. Martin, S. L. Pogue, K. Silver, K. Peng, K. Takatsu, and C. C. Goodnow Enhancement and suppression of signaling by the conserved tail of IgG memory-type B cell antigen receptors J. Exp. Med., April 16, 2007; 204(4): 759 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Paul, A. Nelde, A. Verschoor, and M. C. Carroll Follicular exclusion of autoreactive B cells requires Fc{gamma}RIIb Int. Immunol., April 1, 2007; 19(4): 365 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Barrington, M. Borde, A. Rao, and M. C. Carroll Involvement of NFAT1 in B Cell Self-Tolerance J. Immunol., August 1, 2006; 177(3): 1510 - 1515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Oliver, T. Vass, J. Kappler, and P. Marrack Loss of the proapoptotic protein, Bim, breaks B cell anergy J. Exp. Med., March 20, 2006; 203(3): 731 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Junt, K. Fink, R. Forster, B. Senn, M. Lipp, M. Muramatsu, R. M. Zinkernagel, B. Ludewig, and H. Hengartner CXCR5-Dependent Seeding of Follicular Niches by B and Th Cells Augments Antiviral B Cell Responses J. Immunol., December 1, 2005; 175(11): 7109 - 7116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Reif, K. Okkenhaug, T. Sasaki, J. M. Penninger, B. Vanhaesebroeck, and J. G. Cyster Cutting Edge: Differential Roles for Phosphoinositide 3-Kinases, p110{gamma} and p110{delta}, in Lymphocyte Chemotaxis and Homing J. Immunol., August 15, 2004; 173(4): 2236 - 2240. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
