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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Deets, Katherine A. Higdon, Lauren E. Sze, Kai-yin Friesen, Travis J. Fink, Pamela J. |
| Description | Author Affiliation: Higdon LE ( Department of Immunology and Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98109.); |
| Abstract | Peripheral CD4 T cells in Vß5 transgenic (Tg) C57BL/6J mice undergo tolerance to an endogenous superantigen encoded by mouse mammary tumor virus 8 (Mtv-8) by either deletion or T-cell receptor (TCR) revision. Revision is a process by which surface expression of the Vß5(+) TCR is down-regulated in response to Mtv-8 and recombination activating genes are expressed to drive rearrangement of the endogenous TCRß locus, effecting cell rescue through the expression of a newly generated, non-self-reactive TCR. In an effort to identify the microenvironment in which revision takes place, we show here that the proportion of T follicular helper cells (Tfh) and production of high-affinity antibody during a primary response are increased in Vß5 Tg mice in an Mtv-8-dependent manner. Revising T cells have a Tfh-like surface phenotype and transcription factor profile, with elevated expression of B-cell leukemia/lymphoma 6 (Bcl-6), CXC chemokine receptor 5, programmed death-1, and other Tfh-associated markers. Efficient revision requires Bcl-6 and is inhibited by B lymphocyte-induced maturation protein-1. Revision completes less efficiently in the absence of signaling lymphocytic activation molecule-associated protein although initiation proceeds normally. These data indicate that Tfh formation is required for the initiation of revision and germinal-center interactions for its completion. The germinal center is known to provide a confined space in which B-cell antigen receptors undergo selection. Our data extend the impact of this selective microenvironment into the arena of T cells, suggesting that this fluid structure also provides a regulatory environment in which TCR revision can safely take place. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 15 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gene Rearrangement, T-Lymphocyte Immunology Germinal Center Receptors, Antigen, T-Cell T-Lymphocytes, Helper-Inducer Animals DNA Primers Genetics Flow Cytometry Mice Polymerase Chain Reaction Metabolism Recombination, Genetic Reverse Transcriptase Polymerase Chain Reaction Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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