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Characterization of the Physiologic Function of NF-κB2 p100

Yang, Liqun
http://rave.ohiolink.edu/etdc/view?acc_num=mco1263334529

Abstract Details

2009, Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, College of Medicine.
Proteolytic processing of the NF-κB2 precursor protein p100 generates the active NF-κB2 subunit p52, which in turn transcriptionally upregulates p100 expression. p100 also functions as an IκB molecule capable of repressing p52 activity. The biological significance of this negative feedback control loop has yet to be demonstrated. Here we show that mice deficient in p100 but with constitutive expression of p52 in lymphocyte developed fatal lung inflammation characterized by diffuse alveolar damage with perivascular and peribronchial fibrosis. This is in contrast to their p52-expressing littermates with wild-type p100 alleles, which developed mild lung inflammation with perivascular lymphocyte infiltration and had a normal life span. The fatal lung inflammation probably results from an ongoing T-helper-1 immune response, leading to high-level induction of IFN-λ and its inducible inflammatory chemokines. These findings demonstrate the physiological relevance of the NF-κB2 p100 precursor protein in limiting the potentially detrimental effects of constitutive NF-κB2 signaling in lymphocytes.NF-κB2 plays a crucial role in the lymphocytes and lymphoid organ development. Previous studies with NF-κB2-/- mice present a marked decrease in the peripheral B cell population, loss of inguinal lymph nodes, an absence of discrete perifollicular marginal and mantle zones, and of germinal centers in the spleen. Our analysis of the phenotypes of NF-κB2 p52-Tg mice with or without the NF-κB2 p100 precursor protein provides new insight into the role of NF-κB2 in the regulation of cell populations involved in periphery lymphoid organ development. We show that NF-κB2 p52 is responsible for the normal development of B cells which are essential for the formation of B-cell follicles, germinal centers, follicular dendritic cells networks and marginal zones in the spleen. These findings define a physiological function of NF-κB2 p52 in the development of the mouse immune system.
Han Fei Ding, M.D., Ph.D. (Committee Chair)
Z. Kevin Pan, M.D., Ph.D. (Committee Member)
Dorothea Sawicki, Ph.D. (Committee Member)
James Trempe, Ph.D. (Committee Member)
Ivana de la Serna, Ph.D. (Committee Member)
156 p.
Animal Diseases; Animals; Cellular Biology; Molecular Biology
NF-kB2; lymphoid organs; lung inflammation; germinal center; B cells; follieular dentric cell

Recommended Citations

Citations

  • Yang, L. (2009). Characterization of the Physiologic Function of NF-κB2 p100 [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1263334529

    APA Style (7th edition)

  • Yang, Liqun. Characterization of the Physiologic Function of NF-κB2 p100. 2009. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1263334529.

    MLA Style (8th edition)

  • Yang, Liqun. "Characterization of the Physiologic Function of NF-κB2 p100." Doctoral dissertation, University of Toledo, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=mco1263334529

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.