| 1. |
- Sakata, Naoki, et al.
(författare)
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Differential activation and regulation of mitogen activated protein kinases through the antigen receptor and CD40 in human B cells
- 1999
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Ingår i: European Journal of Immunology. - 0014-2980 .- 1521-4141. ; 29:9, s. 2999-3008
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Tidskriftsartikel (refereegranskat)abstract
- In human B cells, antigen receptor ligation and CD40 ligation are known to activate the extracellular-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) pathways, which in turn regulate many important B cell functions. We previously reported that antigen receptor ligation activated the ERK pathway whereas CD40 ligation activated the JNK/stress-activated protein kinase (SAPK) pathway. Here, we demonstrate that another SAPK, p38/Hog1, is activated by both antigen receptor ligation or CD40 ligation in a human B-lymphoblastoid cell line and tonsillar B cells. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, partially inhibited ERK2 and p38 activation triggered through the B cell receptor whereas activation of JNK1 and p38 through CD40 was not affected. PD98059, a specific inhibitor of mitogen-activated extracellular response kinase kinase (MEK), significantly inhibited ERK2 activation and partially inhibited p38 activation triggered by anti-IgM antibody treatment, but did not affect CD40-dependent signaling events. In addition, anti-IgM antibody-induced signaling pathways were shown to be PKC-dependent in contrast to the CD40-induced signaling pathways. Thus, the B cell receptor and CD40 recruit the ERK, JNK and p38 pathways by using different upstream effectors.
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| 2. |
- Sakata, Naoki, et al.
(författare)
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Differential regulation of CD40-mediated human B cell responses by antibodies directed against different CD40 epitopes
- 2000
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Ingår i: Cellular Immunology. - : Elsevier BV. - 0008-8749 .- 1090-2163. ; 201:2, s. 109-123
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Tidskriftsartikel (refereegranskat)abstract
- Ligation of CD40 using anti-CD40 or soluble CD40-ligand activates numerous intracellular kinases which transduce signals to the nucleus. The nature whereby these signaling events are coupled to distal functional events in B cells is poorly understood. In this study, using anti-CD40 monoclonal antibodies which recognize different epitopes on CD40, we compare the ability to activate the stress-activated protein kinases (SAPK) such as c-Jun NH(2) terminal kinase and p38 in human B cells with CD40 function. Activation of the SAPK pathway correlated with levels of activation of Rel/NF-kappaB transcription factors, but did not appear to be associated with rescue from anti-IgM induced apoptosis by suppressing caspase (CPP32) activity. Somewhat surprisingly, in the presence of IL-4, those antibodies to CD40 which failed to activate SAPK were most active in IgE production. IgE production was augmented in the presence of wortmannin. These studies suggest that rescue from apoptosis and IgE production mediated via CD40 may be independent of SAPK activation, induction of Rel/NF-kappaB, or suppression of CPP32 and that IgE production is, at least in part, regulated by signaling pathways that are dependent on phosphatidylinositol 3-kinase.
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