Distinct mechanisms for rescue from apoptosis in Ramos human B cells by signaling through CD40 and interleukin-4 receptor: role for inhibition of an early response gene, Berg36.
The role of interleukin-4 (IL-4) and CD40 signaling in negative regulation of apoptosis in human Ramos B cells induced in response to different agents was investigated. CD40 ligation protected cells from apoptosis induced by calcium ionophore through an initial, rapid and apparently Bcl-2-independent mechanism, associated with up-regulation of Bcl-XL. However, rescue from apoptosis induced by inhibition of macromolecular synthesis required several hours of prior stimulation with CD40 ligand/antibody and was accompanied by up-regulation of Bcl-2. In contrast, IL-4 did not up-regulate Bcl-2 or Bcl-XL and did not inhibit apoptosis induced by inhibitors of macromolecular synthesis. However, IL-4 did protect Ramos cells from apoptosis induced by calcium ionophore and this effect was accompanied by inhibition of ionophore-induced expression of an immediate early gene encoding a 36-kDa zinc-finger protein, Berg36. Antisense blockade of Berg36 expression partially inhibited ionophore-induced apoptosis to an extent commensurate with the level of IL-4 protection, implicating Berg36 function as a requirement for apoptosis induced through calcium signaling and as a target for IL-4 through which this cytokine inhibits apoptosis in Ramos B cells. These distinct mechanisms for rescue from apoptosis by CD40 and IL-4 may help explain the co-operative roles of these T cell-derived signals for B cell survival.
Infection and Immunity Research group, King's College London, GB.
Z Q
ZQ
Ning
J D
JD
Norton
J
J
Li
J J
JJ
Murphy
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D002051:Burkitt Lymphoma; D051817:Butyrate Response Factor 1; D019013:CD40 Antigens / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017781:Genes, Immediate-Early; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000502:physiology*; D019948:Receptors, Interleukin-4; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D015703:Antigens, CD; D051817:Butyrate Response Factor 1; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; C102034:ZFP36L1 protein, human; D002118:Calcium