Kinetics and signaling requirements of CD40‐mediated protection from B cell receptor‐induced apoptosis

Eeva, Jonna; Postila, Ville; Mättö, Mikko; Nuutinen, Ulla; Ropponen, Antti; Eray, Mine; Pelkonen, Jukka

doi:10.1002/eji.200324227

Cited by 20 publications

(23 citation statements)

References 35 publications

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“…However, our data suggest that activation of these MAP kinase signaling pathways is not significantly affected in CARMA1 KO B cells and not likely a reason for the defective proliferation. Some studies have shown that CD40 stimulation rescues growth arrest and apoptosis in activated B cells [51,52]. Despite defective proliferation upon CD40 stimulation, CARMA1-deficient B cells show normal apoptosis upon stimulation when compared to WT cells (Fig.…”

Section: Discussionmentioning

confidence: 91%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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NF‐κB activation through B cell receptor (BCR) ligation is critical for B cell development, survival and antigen‐mediated activation of B cells. CARD domain and MAGUK‐domain containing protein‐1 (CARMA1), recently identified adaptor molecule, has been shown to play an essential role in BCR‐induced NF‐κB activation. CARMA1‐deficient B cells fail to proliferate upon BCR stimulation, leading to defective humoral responses. Surprisingly, CARMA1‐deficient B cells are also defective in CD40‐induced proliferation. The mechanisms responsible for CD40‐induced proliferation defect have not yet been characterized. In this study, we show that signaling cascades activated by CD40 stimulation are largely unaffected in CARMA1‐deficient B cells. Instead, we have found that the defective proliferation of CARMA1‐deficient B cells is due to two events. First, CARMA1‐deficient B cells show defective cell‐cycle progression. Secondly, the numbers of marginal zone (MZ) B cells, which are the main responders upon CD40 stimulation, are greatly diminished in CARMA1‐deficient mice. Since B cell maturation requires basal signaling through BCR and NF‐κB activation, we propose that impaired BCR signaling in CARMA1‐deficient mice leads to defective maturation of MZ B cell population, which in turn, contributes to impaired proliferation upon CD40 stimulation.

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Section: Discussionmentioning

confidence: 91%

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Pappu¹,

Lin²

2006

Eur J Immunol

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“…HF1A3 cells express surface IgG, and the cells die by apoptosis after surface IgG triggering [28,33]. Thus, it was not surprising that the F(ab') 2 fragments directed against the heavy chain of the IgG induced apoptosis in HF1A3 cells (Fig.…”

Section: The Kinetics Of Rituximab-induced Apoptotic Changesmentioning

confidence: 97%

“…Mitochondrial and cytosolic fractions were separated by an Apoalert cell fractionation kit (Clontech) as described previously [33]. The protein concentration of the lysates was measured with a Bio-Rad DC Protein Assay (Bio-Rad, Hercules, CA) and samples were equalised to contain the same amount of protein with SDS-PAGE buffer containing 0.125 M Tris-Cl pH 6.8, 4% SDS, 20% glycerol, 10% 2-mercaptoethanol, and bromophenol blue.…”

Section: Western Blottingmentioning

confidence: 99%

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The involvement of mitochondria and the caspase-9 activation pathway in rituximab-induced apoptosis in FL cells

et al. 2009

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Despite the wide use of anti-CD20 antibody rituximab in the cancer treatment of B cell malignancies, the signalling pathways of CD20-induced apoptosis are still not understood. By using dominant negative (DN)-caspase-9 overexpressing follicular lymphoma cells we demonstrated that the activation of caspase-9 was essential for rituximab-mediated apoptosis. The death receptor pathway mediated by caspase-8 activation was not involved in rituximab-mediated apoptosis since overexpression of FLIP(short) or FLIP(long) proteins, inhibitors of caspase-8 activation, could not inhibit rituximab-induced apoptosis. However, the death receptor pathway activation by anti-Fas antibodies showed an additive effect on rituximab-induced apoptosis. The stabilisation of the mitochondrial outer membrane by Bcl-x(L) overexpression inhibited cell death, showing the important role of mitochondria in rituximab-induced apoptosis. Interestingly, the rituximab-induced release of cytochrome c and collapse of mitochondrial membrane potential were regulated by caspase-9. We suggest that caspase-9 and downstream caspases may feed back to mitochondria to amplify mitochondrial disruption during intrinsic apoptosis.

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“…The cross-linking of surface immunoglobulin also induces apoptosis in cell lines with an immature B-cell phenotype such as WEHI-231 cells [11,44]. However, using a human follicular lymphoma cell line and a Burkitt lymphoma cell line as an in vitro model, apoptotic signaling events occurring before mitochondrial dysfunction have been demonstrated to be totally reversed by anti-apoptotic signaling, such as CD40 stimulation [26,64]. The cognate interaction between CD40 expressed on B-cell and CD40 ligand (CD154) expressed on helper T-cell induces the expression of the proto-oncogene Bcl-2 that acts as a repressor of apoptosis [61].…”

Section: Apoptosis Of B-cell In Ileal and Jejunal Ppmentioning

confidence: 99%

The sheep and cattle Peyer’s patch as a site of B-cell development

et al. 2006

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-In sheep and cattle, the ileal Peyer's patch (PP), which extends one-two meters along the terminal small intestine, is a primary lymphoid organ of B-cell development. B-cell diversity in the ileal PP is thought to develop by combinatorial mechanisms, gene conversion and/or point mutation. These species also have jejunal PP that function more like secondary lymphoid tissues concerned with mucosal immune reactions. These two types of PP differ significantly in their histology, ontogeny and the extent of lymphocyte traffic. The prenatal development of follicles in the PP begins first in the jejunum during the middle of gestation and then in the ileum during late gestation. B-cells proliferate rapidly in the ileal PP follicle; up to five percent of these cells survive while the majority dies by apoptosis, perhaps driven by the influence of environmental antigen and/ or self-antigen. The surviving cells migrate from the ileal PP and populate the peripheral B-cell compartment. By adolescence, the ileal PP has involuted but the function of jejunal PP, compatible with a role as secondary lymphoid organ, continues throughout life. In this review, we focus on the development of PP as a site of B-cell repertoire generation, positive and negative B-cell selection, and the differences between ileal PP and jejunal PP.

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Kinetics and signaling requirements of CD40‐mediated protection from B cell receptor‐induced apoptosis

Cited by 20 publications

References 35 publications

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

Potential role of CARMA1 in CD40‐induced splenic B cell proliferation and marginal zone B cell maturation

The involvement of mitochondria and the caspase-9 activation pathway in rituximab-induced apoptosis in FL cells

The sheep and cattle Peyer’s patch as a site of B-cell development

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