Shifting control of immunoglobulin heavy chain gene expression.
Item
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Title
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Shifting control of immunoglobulin heavy chain gene expression.
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Identifier
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AAI9959212
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identifier
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9959212
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Creator
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Ong, Jane Hoon Yean.
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Contributor
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Adviser: Laurel Eckhardt
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Date
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2000
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Health Sciences, Immunology
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Abstract
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Regulation of IgH gene expression is tightly controlled during B cell development. Crucial to this regulation is a group of B-cell specific enhancers; the intronic (Emu) and several 3' enhancers {lcub}Calpha3 'E (WA), 3'alphaE (hs1,2), hs3B, hs4{rcub} found embedded both upstream and downstream of the constant gene exons of the murine heavy chain gene locus.;To define the activities and inter-relationships of the enhancer elements in the lgH locus, constructs housing various enhancer combinations placed at a distance from a luciferase reporter gene controlled by a genuine V H promoter were created and transiently transfected into B-cell lines representing various stages of development. The results from these transfections show that the intronic enhancer, Emu, is active throughout B-cell development at relatively constant levels. In contrast, the 3' IgH enhancers when assayed alone, show very little activity at any stage of B cell differentiation. However, and more importantly, when the 3' IgH enhancers are combined, they have little or no activity in pre-B cells, are strongly active in B cells and moderately active in plasma cells. Therefore, unlike Emu, the 3' IgH enhancers show a clear change in activity over the course of B-cell development, with their relative contribution to overall IgH expression being low in early B-cell development, very high at the surface Ig+ stage and roughly similar to Emu at the plasma cell stage.;Further examinations using different enhancer pairs showed that the functions attributed to each pair changes over the. course of B cell differentiation. More enhancer pairs exhibit synergies in Raji cells, very few in S194 and intermediate numbers in M12.4.1 cells.;Taken together, these data comprise the first comprehensive examination of all the known IgH enhancer elements throughout B-cell development.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
