Abstract/Details

The transcription factor Zfx regulates lymphocyte development and homeostasis


2008 2008

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Abstract (summary)

The development, maintenance, and function of lymphocytes involve multiple rounds of antigen (Ag) receptor-induced proliferation followed by prolonged survival in the quiescent state. We tested the role of the transcription factor Zfx, a recently identified regulator of stem cell survival, in lymphocyte development and homeostasis. Conditional Zfx deletion in the T cell lineage resulted in a partial block at the double-negative to double-positive transition in thymocyte development and led to the impaired survival of naïve T cells in the periphery. Ablation of Zfx in the B cell lineage blocked the pre-BI/pre-BII cell transition in the bone marrow and impaired the generation of the B-1 B cell lineage. Zfx-deficient peripheral B cells showed accelerated turnover, depletion of mature recirculating B cells, reduced germinal center formation, and delayed antibody responses. The loss of Zfx did not affect BCR-mediated proximal signaling, yet impaired BCR-induced proliferation and survival. Genome-wide expression analysis revealed the aberrant induction of the integrated stress response in BCR-activated Zfx-deficient B cells. These data suggest that Zfx controls both Ag receptor-induced proliferation and peripheral homeostasis of mature lymphocytes. In mature B cells, this is achieved at least in part by restraining the stress response following BCR signaling.

Indexing (details)


Subject
Cellular biology;
Microbiology;
Immunology
Classification
0379: Cellular biology
0410: Microbiology
0982: Immunology
Identifier / keyword
Health and environmental sciences; Biological sciences; Antigen receptors; Homeostasis; Integrated stress response; Lymphocyte development; Lymphocyte homeostasis; Lymphocytes; Zfx
Title
The transcription factor Zfx regulates lymphocyte development and homeostasis
Author
Arenzana, Teresita L.
Number of pages
176
Publication year
2008
Degree date
2008
School code
0054
Source
DAI-B 69/10, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549854869
Advisor
Reizis, Boris
University/institution
Columbia University
University location
United States -- New York
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3333298
ProQuest document ID
304623851
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304623851
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