Characterization of the molecular and immunoregulatory properties of IgD -receptors expressed on T lymphocytes.
Item
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Title
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Characterization of the molecular and immunoregulatory properties of IgD -receptors expressed on T lymphocytes.
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Identifier
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AAI9986395
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identifier
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9986395
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Creator
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Wu, Yan.
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Contributor
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Adviser: Richard F. Coico
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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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Health Sciences, Immunology
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Abstract
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Since its discovery, the biologic role of immunoglobulin D (IgD) has remained enigmatic despite numerous experimental attempts to define its function. IgD is a predominant surface immunoglobulin (Ig) expressed in high density on mature, resting B lymphocytes along with IgM. Previous studies have shown that (1) receptors specific for IgD (IgD-R) are expressed by human CD4 + and CD8+ T cells whereas IgD-R appear to be restricted to the CD4+ T cell population in mouse; (2) injection of oligomeric IgD in mice results in rapid increase in the number of CD4 + IgD-R+ T cells (∼30%); (3) several other stimuli that activate T cells also induced upregulation of IgD-R; (4) in vitro studies have confirmed that cognate interactions between T and B cells are required to demonstrate enhanced helper activity using T cells with upregulated IgD-receptors (IgD-R). The goal of the current study was to assess the role of antigen-presenting B cells on IgD-R+ T cell activation. We compared B cells from IgD+/+, IgD+/--, and IgD--/-- mice to determined whether IgD expression is prequisite for functional activity of IgD-R+ T cells. Our results revealed that ligation of IgD on B cells and IgD-R on T cells promotes: (1) enhanced antibody responses and clonal expansion of antigen-specific T cells; (2) enhanced cytokine productions both at the protein and mRNA levels, with shift towards the TH2 phenotype; (3) phosphorylation of intracellular proteins; and, (4) enhanced expression of CD28 on T cells. Molecular characterization of IgD-R demonstrated that a ∼29 kDa band is phosphorylated and exhibits stong affinity for biotinylated IgD. In summary, our studies lead us to conclude that IgD-R are, indeed, involved in bidirectional signaling of B and T cells, and the skewing towards the T H2 phenotype following crosslinking of the IgD-R is consistent with the functional properties of IgD-R+ T cells which are known to significantly enhance antibody responses. Finally, studies of Fas antigen regulation and expression associated with upregulation of IgD-R suggest that ligation of IgD-R may protect T cells from undergoing apoptosis following their activation by IgD-expressing B cells. Therefore, IgD-R function not only as a ligand for IgD, but also play an important role in the regulation of humoral immune responses and T cell activation.
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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.
