| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Howard Hughes Medical Institute and
Department of Microbiology and Immunology and Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143
Th cell access to primary B cell follicles is dependent on CXCR5. However, whether CXCR5 induction on T cells is sufficient in determining their follicular positioning has been unclear. In this study, we find that transgenic CXCR5 overexpression is not sufficient to promote follicular entry of naive T cells unless the counterbalancing influence of CCR7 ligands is removed. In contrast, the positioning of Ag-engaged T cells at the B/T boundary could occur in the absence of CXCR5. The germinal center (GC) response was 2-fold reduced when T cells lacked CXCR5, although these T cells were able to access the GC. Finally, CXCR5highCCR7low T cells were found to have elevated IL-4 transcript and programmed cell death gene-1 (PD-1) expression, and PD-1high cells were reduced in the absence of T cell CXCR5 or in mice compromised in GC formation. Overall, these findings provide further understanding of how the changes in CXCR5 and CCR7 expression regulate Th cell positioning during Ab responses, and they suggest that development and/or maintenance of a PD-1high follicular Th cell subset is dependent on appropriate interaction with GC B cells.
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 Grant AI45093. N.M.H. was supported by the National Health and Medical Research Council of Australia CJ Martin Fellowship; C.D.C.A. was supported by a Howard Hughes Medical Institute predoctoral fellowship. J.G.C. is an investigator of the Howard Huges Medical Institute.
2 Current address: Peter MacCallum Cancer Institute, Research Division, Locked Bag 1, A’Beckett Street, Melbourne, Victoria, Australia, 8006.
3 Current address: Washington University, Microbiology Department, Box 357242, Seattle, WA 98195.
4 Current address: Center for Blood Research Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.
5 Address correspondence and reprint requests to Dr. Jason G. Cyster, Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0414. E-mail address: Jason.Cyster{at}ucsf.edu
6 Abbreviations used in this paper: GC, germinal center; ASC, Ab-secreting cell; DEL, duck egg lysozyme; FDC, follicular dendritic cell; HEL, hen egg lysozyme; int, intermediate; NP, (4-hydroxy-3-nitrophenyl)acetyl; CGG, chicken 
-globulin; PD-1, programmed cell death gene-1; SDF-1, stromal cell-derived factor.
This article has been cited by other articles:
|
|
 |
|
  C. R. L. Beishuizen, N. A. M. Kragten, L. Boon, M. A. Nolte, R. A. W. van Lier, and K. P. J. M. van Gisbergen Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to Inhibit Germinal Center B Cell Formation through FasL-Fas Interactions J. Immunol., November 15, 2009; 183(10): 6442 - 6451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M'Hidi, M.-L. Thibult, B. Chetaille, F. Rey, R. Bouadallah, R. Nicollas, D. Olive, and L. Xerri High Expression of the Inhibitory Receptor BTLA in T-Follicular Helper Cells and in B-Cell Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia Am J Clin Pathol, October 1, 2009; 132(4): 589 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Johnston, A. C. Poholek, D. DiToro, I. Yusuf, D. Eto, B. Barnett, A. L. Dent, J. Craft, and S. Crotty Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation Science, August 21, 2009; 325(5943): 1006 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Zaretsky, J. J. Taylor, I. L. King, F. A. Marshall, M. Mohrs, and E. J. Pearce T follicular helper cells differentiate from Th2 cells in response to helminth antigens J. Exp. Med., May 11, 2009; 206(5): 991 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. King and M. Mohrs IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells J. Exp. Med., May 11, 2009; 206(5): 1001 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Linterman, R. J. Rigby, Raphael. K. Wong, D. Yu, R. Brink, J. L. Cannons, P. L. Schwartzberg, M. C. Cook, G. D. Walters, and C. G. Vinuesa Follicular helper T cells are required for systemic autoimmunity J. Exp. Med., March 16, 2009; 206(3): 561 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tsuji, N. Komatsu, S. Kawamoto, K. Suzuki, O. Kanagawa, T. Honjo, S. Hori, and S. Fagarasan Preferential Generation of Follicular B Helper T Cells from Foxp3+ T Cells in Gut Peyer's Patches Science, March 13, 2009; 323(5920): 1488 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Achtman, U. E. Hopken, C. Bernert, and M. Lipp CCR7-deficient mice develop atypically persistent germinal centers in response to thymus-independent type 2 antigens J. Leukoc. Biol., March 1, 2009; 85(3): 409 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Velaga, H. Herbrand, M. Friedrichsen, T. Jiong, M. Dorsch, M. W. Hoffmann, R. Forster, and O. Pabst Chemokine Receptor CXCR5 Supports Solitary Intestinal Lymphoid Tissue Formation, B Cell Homing, and Induction of Intestinal IgA Responses J. Immunol., March 1, 2009; 182(5): 2610 - 2619. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
