Abstract
CD40 ligand (CD40L) delivers a contact-dependent signal to B cells which, in the presence of interleukin (IL)-4, drives immunoglobulin isotype switching to IgE. CD40L expression in T cells is transient, requires activation of protein kinase C and a rise in intracellular calcium concentration ([Ca2+]i), and is inhibited by cyclosporin A (CsA). CsA also inhibited T-cell-dependent IL-4-driven IgE synthesis. We have found that expression of CD40L is developmentally regulated. Expression of CD40L was restricted to mature single-positive thymocytes which, in the presence of IL-4, were capable of inducing B cells to undergo IgE isotype switching. CD40L expression was severely decreased in cord blood lymphocytes and was associated with a severely decreased ability to undergo T-cell-dependent IgE isotype switching.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Antigens, CD / physiology
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Antigens, Differentiation, B-Lymphocyte / physiology
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B-Lymphocytes / immunology
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CD40 Antigens
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CD40 Ligand
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Cyclosporine / pharmacology
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Fetal Blood / cytology
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Gene Expression Regulation, Developmental*
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Humans
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Immunoglobulin Class Switching*
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Immunoglobulin E / biosynthesis*
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Infant, Newborn
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Interleukin-4 / antagonists & inhibitors
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Interleukin-4 / pharmacology
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Lymphocyte Cooperation / drug effects
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Thymus Gland / cytology
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Thymus Gland / growth & development
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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CD40 Antigens
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Membrane Glycoproteins
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CD40 Ligand
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Interleukin-4
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Immunoglobulin E
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Cyclosporine