Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
The Cyclin D3 Protein Enforces Monogenic TCRI3 Expression by Mediating TCRβ Protein-Signaled Feedback Inhibition of Vβ Recombination
The Journal of immunology (1950), v 212(4)
15 Feb 2024
PMID: 38117277
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In jawed vertebrates, adaptive immunity depends on the process of V(D)J recombination creating vast numbers of T and B lymphocytes that each expresses unique Ag receptors of uniform specificity. The asynchronous initiation of V-to-(D)J rearrangement between alleles and the resulting protein from one allele signaling feedback inhibition of V recombination on the other allele ensures homogeneous receptor specificity of individual cells. Upon productive VI3-to-DI3JI3 rearrangements in noncycling double -negative thymocytes, TCRI3 protein signals induction of the cyclin D3 protein to accelerate cell cycle entry, thereby driving proliferative expansion of developing aI3 T cells. Through undetermined mechanisms, the inactivation of cyclin D3 in mice causes an increased frequency of aI3 T cells that express TCRI3 proteins from both alleles, producing lymphocytes of heterogeneous specificities. To determine how cyclin D3 enforces monogenic TCRI3 expression, we used our mouse lines with enhanced rearrangement of specific VI3 segments due to replacement of their poor -quality recombination signal sequence (RSS) DNA elements with a better RSS. We show that cyclin D3 inactivation in these mice elevates the frequencies of aI3 T cells that display proteins from RSS-augmented VI3 segments on both alleles. By assaying mature aI3 T cells, we find that cyclin D3 deficiency increases the levels of VI3 rearrangements that occur within developing thymocytes. Our data demonstrate that a component of the cell cycle machinery mediates TCRI3 protein -signaled feedback inhibition in thymocytes to achieve monogenic TCRI3 expression and resulting uniform specificity of individual aI3 T cells. The Journal of Immunology, 2024, 212: 534-540.
Metrics
Details
- Title
- The Cyclin D3 Protein Enforces Monogenic TCRI3 Expression by Mediating TCRβ Protein-Signaled Feedback Inhibition of Vβ Recombination
- Creators
- Erica J. Culberson - Children's Hospital of PhiladelphiaKymberle C. Shields - University of PennsylvaniaRebecca A. Glynn - University of PennsylvaniaBrittney M. Allyn - University of PennsylvaniaKatharina E. Hayer - Raymond and Ruth Perelman School of Medicine at the University of PennsylvaniaCraig H. Bassing - University of Pennsylvania
- Publication Details
- The Journal of immunology (1950), v 212(4)
- Publisher
- American Association of Immunologists
- Number of pages
- 8
- Grant note
- RO1 AI143661 / Division of Intramural Research, National Institute of Allergy and Infectious Diseases Grant
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001167616900010
- Scopus ID
- 2-s2.0-85184298422
- Other Identifier
- 991021861208104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology