Expression of the CD40 ligand in T lymphocytes and induction of IgE isotype switching.
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.
Fuleihan
R
R
Division of Immunology, Children's Hospital, Boston, Mass., USA.
Ahern
D
D
Geha
R S
RS
D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D023201:CD40 Ligand; D016572:Cyclosporine / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007231:Infant, Newborn; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D016572:Cyclosporine