Minimal cross-linking and epitope requirements for CD40-dependent suppression of apoptosis contrast with those for promotion of the cell cycle and homotypic adhesions in human B cells

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dc.contributor.authorPound, J. D.en
dc.contributor.authorChalla, A.en
dc.contributor.authorHolder, M. J.en
dc.contributor.authorArmitage, R. J.en
dc.contributor.authorDower, S. K.en
dc.contributor.authorFanslow, W. C.en
dc.contributor.authorKikutani, H.en
dc.contributor.authorPaulie, S.en
dc.contributor.authorGregory, C. D.en
dc.contributor.authorGordon, J.en
dc.date.accessioned2015-11-24T19:04:19Z
dc.date.available2015-11-24T19:04:19Z
dc.identifier.issn0953-8178-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/20019
dc.rightsDefault Licence-
dc.subjectAntigens, CD40/*immunologyen
dc.subject*Apoptosisen
dc.subjectB-Lymphocytes/cytology/*immunologyen
dc.subjectBinding, Competitiveen
dc.subjectCD40 Liganden
dc.subjectCell Adhesionen
dc.subjectCell Cycleen
dc.subjectEpitope Mappingen
dc.subjectEpitopesen
dc.subjectGerminal Center/cytology/*immunologyen
dc.subjectHumansen
dc.subjectImmunologic Cappingen
dc.subject*Lymphocyte Activationen
dc.subjectMembrane Glycoproteinsen
dc.titleMinimal cross-linking and epitope requirements for CD40-dependent suppression of apoptosis contrast with those for promotion of the cell cycle and homotypic adhesions in human B cellsen
heal.abstractEight different CD40 mAb shared with soluble trimeric CD40 ligand (sCD40LT) the capacity to rescue germinal center (GC) B cells from spontaneous apoptosis and to suppress antigen receptor-driven apoptosis in group I Burkitt's lymphoma cells. Three mAb (G28-5, M2 and M3) mimicked sCD40LT in its ability to promote strong homotypic adhesion in resting B cells, whereas others (EA5, BL-OGY/C4 and 5C3) failed to stimulate strong clustering. Binding studies revealed that only those mAb that promoted strong B cell clustering bound at, or near to, the CD40L binding site. While all eight mAb and sCD40LT were capable of synergizing with IL-4 or phorbol ester for promoting DNA synthesis in resting B cells, co-stimulus-independent activation of the cells into cycle through CD40 related directly to the extent of receptor cross-linking. Thus, mAb which bound outside the CD40L binding site synergized with sCD40LT for promoting DNA synthesis; maximal levels of stimulation were achieved by presenting any of the mAb on CD32 transfectants in the absence of sCD40LT or by cross-linking bound sCD40LT with a second antibody. Monomeric sCD40L, which was able to promote rescue of GC B cells from apoptosis, was unable to drive resting B cells into cycle. These studies demonstrate that CD40-dependent rescue of human B cells from apoptosis requires minimal cross-linking and is essentially epitope independent, whereas the requirements for promoting cell cycle progression and homotypic adhesion are more stringent. Possible mechanisms underlying these differences and their physiological significance are discussed.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/10050669-
heal.identifier.secondaryhttp://intimm.oxfordjournals.org/content/11/1/11.full.pdf-
heal.journalNameInt Immunolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate1999-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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