Journal Article10.1002/EJI.1830240118
Induction of B cell costimulatory function by recombinant murine CD40 ligand.
Mary K. Kennedy,Kendall M. Mohler,Kurt D. Shanebeck,Peter Robert Baum,Kathleen S. Picha,Carol Otten-Evans,Charles A. Janeway,Kenneth H. Grabstein +7 more
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TL;DR: It is shown that recombinant membrane‐bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4+ Tcells and suggested that CD40 L‐activated B cells express an additional costimulation activity that is not associated with LPS‐ activated B cells.
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Abstract: T cell-dependent regulation of B cell growth and differentiation involves an interaction between CD40, a B cell surface molecule, and the CD40 ligand (CD40L) which is expressed on activated CD4+ T cells. In the current study, we show that recombinant membrane-bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4+ T cells. CD40L- or lipopolysaccharide (LPS)-activated, but not control-cultured B cells were strong costimulators of anti-CD3 or alloantigen-dependent T cell responses. The molecular interactions responsible for the increased costimulatory functions were examined by analyzing the activated B cells for changes in the expression of two costimulatory molecules, B7 and heat-stable antigen (HSA), as well as by the use of antagonists of B7 and HSA (CTLA4.Fc and 20C9, respectively). The expression of both B7 and HSA was enhanced on B cells activated with LPS. As observed in previous studies, the costimulatory activity of the LPS-activated B cells was dependent on both B7 and HSA and was completely inhibited in the presence of a combination of CTLA4.Fc and 20C9. In contrast, activation of B cells with CD40L induced the expression of B7 but did not enhance the expression of HSA. In addition the costimulatory activity of the CD40L-activated B cells was partially, but not completely, inhibited by the combination of CTLA4.Fc and 20C9. These results demonstrate that CD40L regulates costimulatory function of B cells in part by inducing the expression of B7 and suggest that CD40L-activated B cells express an additional costimulatory activity that is not associated with LPS-activated B cells.
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Citations
Selective Requirement for CD40-CD154 in Drug-Induced Type 1 Versus Type 2 Responses to Trinitrophenyl-Ovalbumin
Stefan Nierkens,Pauline van Helden,M. Bol,Rob Bleumink,Peter J.S. van Kooten,Seema Ramdien-Murli,Louis Boon,Raymond Pieters +7 more
TL;DR: The findings indicate that the CD40-CD154 costimulatory interaction is a prerequisite in drug-induced type 2 responses and is only marginally involved in type 1 responses.
Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion.
TL;DR: It is demonstrated that the CD40L-CD40 interaction is crucial for the in vivo priming of Th1 T cells via the stimulation of IL-12 secretion by antigen-presenting cells (APC).
The role of CD154 in organ transplant rejection and acceptance
TL;DR: Current literature suggests that CD154 can either stimulate or attenuate an immune response, depending upon the model system under study, and the precise mechanisms by which antibodies against CD154 exert their anti-rejection effects have remained less obvious.
Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.
TL;DR: It is reported that normal human endothelial cells also express CD40 in situ, and CD40L-CD40 interactions induce endothelial cell activation in vitro, suggesting a mechanism by which activated CD4+ T cells may augment inflammatory responses in vivo by upregulating the expression of endothelialcell surface adhesion molecules.
Activated B Cells Express Increased Levels of Costimulatory Molecules in Young Autoimmune NZB and (NZB × NZW)F1 Mice
TL;DR: The levels of B7.1 on the activated B cell population are similar to those induced by CD40 stimulation raising the possibility that activated B cells in NZB and NZB/W mice provide costimulatory signals to self-reactive T cells leading to loss of tolerance.
References
CTLA-4 is a second receptor for the B cell activation antigen B7.
Peter S. Linsley,William E. Brady,Mark Urnes,Laura Sue Grosmaire,Nitin K. Damle,Jeffrey A. Ledbetter +5 more
TL;DR: These findings provide direct evidence that, like its structural homologue CD28, CTLA- 4 is able to bind the B7 counter-receptor on activated B cells.
Clonal Expansion Versus Functional Clonal Inactivation: A Costimulatory Signalling Pathway Determines the Outcome of T Cell Antigen Receptor Occupancy
TL;DR: Etude du controle de la proliferation des lymphocytes T par les cellules presentant l'antigene, examen des signaux biologiques and biochimiques impliques dans ce mecanisme.
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Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation.
Peter S. Linsley,William E. Brady,Laura Sue Grosmaire,Alejandro Aruffo,Nitin K. Damle,Jeffrey A. Ledbetter +5 more
TL;DR: It is demonstrated that the CD28 signaling pathway could be activated by B7, resulting in increased T cell cytokine production and T cell proliferation, and costimulatory for T cell activation.
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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.
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