Role for type 1 interferons in the exclusion of B cells from microphthalmic marrow

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Title Role for type 1 interferons in the exclusion of B cells from microphthalmic marrow
Publication Type thesis
School or College School of Medicine
Department Pathology
Author Roundy, Kirstin Mae
Contributor Smith, R.; Weiss, J.J.; Weis, J.H.
Date 2004-05
Description Previous studies demonstrated an increase RANKL (receptor activator of NF-kB ligand) mRNA and a deficiency of B cells in the bone marrow of the microphthalmic (mi)mouse. We hypothesized that the overexpression of RANKL is a bone hemostatatic response to stimulate osteoclasts to degrade bone and relive the mi osteopetrotic condition. IFN-beta is produced upon RANKL binding through c-fos dependent pathway. In turn, the inductin of IFN-beta serves as a negative regulator of RANKL-induced ostoclastogenesis by production of c-fos and preventing transcription of ostteoclast differentiation genes. In addition to a regulatory function of the bone, TYPE I interferons, including IFN-beta, have been shown to induce apoptosis in B cell in vivo. We hypothesized the IFN-beta, produced by increased RANKL signaling, was responsible for the loss of B cell in the mi bone marrow, This thesis details an investigation to test this hypothesis by determining which cell types contribute to an increase in RANKL expression in the mi marrow and analyzing mice deficient in IFN-? signaling. Thus, it this model is true and IFN-beta in inducing apoptosis of B cells in the mi marrow, mating mi mice with animals that lack the IFN receptor would make bone marrow cell unresponsive to interferon and decrease B cell apoptosis. We did see a significant increase in B cell numbers and a decrease in granulocyte numbers in the marrow of mi IFN-alpha?/betaR KO mice. This study identifies additional roles the TYPE I interferons have in cell development in the mi bone marrow.
Type Text
Publisher University of Utah
Subject Physiology; IFN-beta-Mediated
Subject MESH Bone Marrow; Bone Marrow Cells; Interferon-alpha; Interferon-beta
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "A role for type 1 interferons in the exclusion of B cells from microphthalmic marrow." Spencer S. Eccles Health Sciences Library. Print version of "A role for type 1 interferons in the exclusion of B cells from microphthalmic marrow." available at J. Willard Marriott Library Special Collection. QR6.5 2004 .R68.
Rights Management © Kirstin Mae Roundy.
Format application/pdf
Format Medium application/pdf
Format Extent 1,567,225 bytes
Identifier undthes,4787
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 1,567,291 bytes
ARK ark:/87278/s66w9czv
Setname ir_etd
ID 191743
Reference URL https://collections.lib.utah.edu/ark:/87278/s66w9czv
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