Journal ArticleDOI
Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM
Ulf Korthäuer,Daniel Graf,Hans W. Mages,Francine Brière,M Padayachee,Sue Malcolm,Alberto G. Ugazio,Luigi D. Notarangelo,Roland J. Levinsky,Richard A. Kroczek +9 more
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TLDR
Evidence is presented that point mutations in the TRAP gene give rise to nonfunctional or defective expression of TRAP on the surface of T cells in patients with HIGM1, which is responsible for the observed immunoglobulin isotype defect in HIGm1.Abstract:
X chromosome-linked immunodeficiency with hyper-IgM (HIGM1, MIM number 308230) is a rare disorder characterized by recurrent bacterial infections, very low or absent IgG, IgA and IgE, and normal to increased IgM and IgD serum levels. HIGM1 has been suggested to result from ineffective T-cell help for B cells. We and others have identified a novel, TNF-related activation protein (TRAP) that is exclusively expressed on the surface of stimulated T cells. TRAP, a type II transmembrane protein of M(r) 33,000, is the physiological ligand for CD40 (refs 5-8). Crosslinking of CD40 on B cells induces, in the presence of lymphokines, immunoglobulin class switching from IgM to IgG, IgA or IgE. Mapping of the TRAP gene to the X-chromosomal location q26.3-q27.1 (ref. 6) suggested a causal relationship to HIGM1, which had previously been assigned to Xq26 (refs 12-14). Here we present evidence that point mutations in the TRAP gene give rise to nonfunctional or defective expression of TRAP on the surface of T cells in patients with HIGM1. The resultant failure of TRAP to interact with CD40 on functionally intact B cells is responsible for the observed immunoglobulin isotype defect in HIGM1.read more
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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
CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells
Volker Henn,Joseph R. Slupsky,Michael Gräfe,Ioannis Anagnostopoulos,Reinhold Förster,Gert Müller-Berghaus,Richard A. Kroczek +6 more
TL;DR: In this paper, platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo, indicating that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.
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.
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
Mechanism of antigen-driven selection in germinal centres.
Yong-Jun Liu,Douglas E. Joshua,Gwyn T. Williams,Christopher A. Smith,John Gordon,I. C. M. Maclennan +5 more
TL;DR: It is found that, on culture, centrocytes isolated from human tonsil kill themselves within a few hours by apoptosis, not a feature of other tonsillar B cells.
Journal ArticleDOI
Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.
Thierry Defrance,Béatrice Vanbervliet,Francine Brière,Isabelle Durand,Françoise Rousset,Jacques Banchereau +5 more
TL;DR: The data suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans, and that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes.
Journal ArticleDOI
The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity.
Diane Hollenbaugh,Laura Sue Grosmaire,C.D. Kullas,N J Chalupny,S. Braesch-Andersen,R.J. Noelle,Ivan Stamenkovic,J A Ledbetter,A. Aruffo +8 more
TL;DR: It is suggested that B cells require a second signal besides gp39‐CD40 to drive proliferation and that soluble gp39 alone in a non‐membrane bound form is able to provide co‐stimulatory signals to B cells.
Journal ArticleDOI
CD40 and IgE: synergism between anti-CD40 monoclonal antibody and interleukin 4 in the induction of IgE synthesis by highly purified human B cells.
TL;DR: Although the exact role played by CD40 in IgE responses in vivo remains to be established, this T cell-independent system represents a useful model to characterize the biochemical and molecular events leading to IgE synthesis in human B cells.