Journal ArticleDOI
CD40 ligand mutations in X-linked immunodeficiency with hyper-IgM
TLDR
CD40L transcripts in four unrelated male children with the hyper-IgM syndrome showed either deletions or point mutations clustered within a limited region of the CD40L extracellular domain provide a molecular basis for immunoglobulin isotype switch defects observed in this immunodeficiency.Abstract:
Signalling for the B-cell immunoglobulin isotype switch requires T-cell-derived cytokines and T-B cell interaction, which operates primarily through the CD40 molecule on B cells with its ligand (CD40L) on activated T cells (reviewed in ref. 1). The CD40L is a type II membrane protein with homology to tumour necrosis factor-alpha and -beta, and has important functions in B-cell activation and differentiation. Human CD40L maps on Xq26.3-27.1 (ref. 3), the region where a primary immunodeficiency characterized by an immunoglobulin isotype switch defect (the hyper-IgM immunodeficiency syndrome, HIGM1) has been localized. The hypothesis that HIGM1 involves an abnormality of the CD40L has been tested. We report here the lack of CD40L expression in four unrelated male children with the hyper-IgM syndrome. CD40L transcripts in these patients showed either deletions or point mutations clustered within a limited region of the CD40L extracellular domain. These genetic alterations with abnormal CD40L expression provide a molecular basis for immunoglobulin isotype switch defects observed in this immunodeficiency.read more
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Journal ArticleDOI
Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme
Masamichi Muramatsu,Kazuo Kinoshita,Sidonia Fagarasan,Shuichi Yamada,Yoichi Shinkai,Tasuku Honjo +5 more
TL;DR: Results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in CH12F3-2 B lymphoma.
Journal ArticleDOI
Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).
Patrick Revy,Taro Muto,Yves Levy,Frederic Geissmann,Alessandro Plebani,Ozden Sanal,Nadia Catalan,Monique Forveille,Dufourcq-Lagelouse R,Andrew R. Gennery,Ilhan Tezcan,Fügen Ersoy,Hülya Kayserili,Alberto G. Ugazio,Nicole Brousse,Masamichi Muramatsu,Luigi D. Notarangelo,Kazuo Kinoshita,Tasuku Honjo,Alain Fischer,Anne Durandy +20 more
TL;DR: The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.
Journal ArticleDOI
Activation of human dendritic cells through CD40 cross-linking.
Christophe Caux,Catherine Massacrier,Béatrice Vanbervliet,Bertrand Dubois,C. van Kooten,Isabelle Durand,Jacques Banchereau +6 more
TL;DR: It is demonstrated that dendritic Langerhans cells (D-Lc) generated by culturing cord blood CD34+ progenitor cells with granulocyte/macrophage colony-stimulating and tumor necrosis factor alpha (TNF-alpha) express functional CD40 at a density higher than that found on B cells.
Journal ArticleDOI
The CD40 Antigen and its Ligand
Jacques Banchereau,F Bazan,D Blanchard,Francine Brière,Jean-Pierre Galizzi,C. van Kooten,Yong-Jun Liu,Françoise Rousset,Sem Saeland +8 more
TL;DR: As other members of the tumor necrosis factor receptor family have been shown to bind several ligands, it is possible that CD40 may bind other ligands that may trigger CD40 on different cell types such as hematopoietic cells or epithelial cells.
References
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Journal ArticleDOI
Molecular and biological characterization of a murine ligand for CD40
Richard J. Armitage,William C. Fanslow,Laura Strockbine,Timothy A. Sato,Ky N. Clifford,Brian M. Macduff,Dirk M. Anderson,Steven D. Gimpel,Terri Davis-Smith,Charles R. Maliszewski,Edward A. Clark,Craig A. Smith,Kenneth H. Grabstein,David Cosman,Melanie K. Spriggs +14 more
TL;DR: The cloning of a ligand for CD40 that is expressed on the cell surface of activated T cells and mediates B-cell proliferation in the absence of co-stimulus, as well as IgE production in the presence of interIeukin-4 is reported.
Journal ArticleDOI
A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells
Randolph J. Noelle,Meenakshi Roy,David M. Shepherd,Ivan Stamenkovic,Jeffrey A. Ledbetter,Alejandro Aruffo +5 more
TL;DR: Data indicate that the 39-kDa membrane protein expressed on activated Th is a binding protein for CD40 and functions to transduce the signal for Th-dependent B-cell activation.
Journal ArticleDOI
Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity.
Patrick W. Gray,Bharat B. Aggarwal,Charles V. Benton,Timothy S. Bringman,William J. Henzel,Julie A. Jarrett,David W. Leung,Barbara Moffat,Peter Ng,L. P. Svedersky,Michael A. Palladino,Glenn Evan Nedwin +11 more
TL;DR: Purified recombinant lymphotoxin shows cytotoxic activity on murine and human tumour cell lines in vitro and causes necrosis of certain murine sarcomas in vivo.
Journal ArticleDOI
Molecular cloning of the complementary dna for human tumor necrosis factor
Alice M. Wang,Abla A. Creasey,M. B. Ladner,Leo S. Lin,James E. Strickler,JN Van Arsdell,R Yamamoto,David F. Mark +7 more
TL;DR: Human TNF was purified to apparent homogeneity as a 17.3-kilodalton protein from HL-60 leukemia cells and showed cytotoxic and cytostatic activities against various human tumor cell lines.
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The structure of tumor necrosis factor-alpha at 2.6 A resolution. Implications for receptor binding.
Michael J. Eck,Stephen R. Sprang +1 more
TL;DR: The three-dimensional structure of tumor necrosis factor (TNF-alpha), a protein hormone secreted by macrophages, has been determined and striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus is revealed.