Lipopolysaccharide Protects Primary B Lymphocytes from Apoptosis by Preventing Mitochondrial Dysfunction and Bax Translocation to Mitochondria

Souvannavong, Vongthip; Lemaire, Christophe; Chaby, Richard

doi:10.1128/iai.72.6.3260-3266.2004

Cited by 19 publications

(15 citation statements)

References 47 publications

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“…5, B and C). LPS activates antiapoptotic signaling via NF-B and protects primary mouse spleen B cells from spontaneous and staurosporin-induced apoptosis (57). Therefore, the antiapoptotic activities induced by LPS seem to override the proapoptotic TGF-␤-induced signaling.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Exon I of SMAD7 in Mice Results in Altered B Cell Responses

Rosendahl

Brodin

et al. 2006

The Journal of Immunology

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The members of the TGF-β superfamily, i.e., TGF-β isoforms, activins, and bone morphogenetic proteins, regulate growth, differentiation, and apoptosis, both during embryonic development and during postnatal life. Smad7 is induced by the TGF-β superfamily members and negatively modulates their signaling, thus acting in a negative, autocrine feedback manner. In addition, Smad7 is induced by other stimuli. Thus, it can fine-tune and integrate TGF-β signaling with other signaling pathways. To investigate the functional role(s) of Smad7 in vivo, we generated mice deficient in exon I of Smad7, leading to a partial loss of Smad7 function. Mutant animals are viable, but significantly smaller on the outbred CD-1 mouse strain background. Mutant B cells showed an overactive TGF-β signaling measured as increase of phosphorylated Smad2-positive B cells compared with B cells from wild-type mice. In agreement with this expected increase in TGF-β signaling, several changes in B cell responses were observed. Mutant B cells exhibited increased Ig class switch recombination to IgA, significantly enhanced spontaneous apoptosis in B cells, and a markedly reduced proliferative response to LPS stimulation. Interestingly, LPS treatment reverted the apoptotic phenotype in the mutant cells. Taken together, the observed phenotype highlights a prominent role for Smad7 in development and in regulating the immune system’s response to TGF-β.

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Section: Discussionmentioning

confidence: 99%

Deletion of Exon I of SMAD7 in Mice Results in Altered B Cell Responses

Rosendahl

Brodin

et al. 2006

The Journal of Immunology

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“…The balance between activation signals, apoptosis-inducing signals, and survival signals is notable in B cells. Mature B cells undergo spontaneous apoptosis in vitro, and their survival requires cytokines or antigenic stimulation (3,4). B cell activation by anti-IgM Ab induces B cell proliferation; however, BCR multimerization of surface Ig also can induce apoptosis (5,6).…”

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confidence: 99%

Heat Shock Protein 60, via MyD88 Innate Signaling, Protects B Cells from Apoptosis, Spontaneous and Induced

Cohen-Sfady

Pevsner‐Fischer

Margalit

et al. 2009

The Journal of Immunology

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We recently reported that heat shock protein 60 (HSP60) via TLR4 signaling activates B cells and induces them to proliferate and secrete IL-10. We now report that HSP60 inhibits mouse B cell apoptosis, spontaneous or induced by dexamethasone or anti-IgM activation. Unlike HSP60 enhancement of B cell proliferation and IL-10 secretion, TLR4 signaling was not required for the inhibition of apoptosis by HSP60; nevertheless, MyD88 was essential. Inhibition of apoptosis by HSP60 was associated with up-regulation of the antiapoptotic molecules Bcl-2, Bcl-xL, and survivin, maintenance of the mitochondrial transmembrane potential, and inhibition of caspase-3 activation. Moreover, B cells incubated with HSP60 manifested prolonged survival following transfer into recipient mice. These results extend the varied role of HSP60 in the innate regulation of the adaptive immune response.

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“…In the immune system, apoptosis plays a fundamental role in the development and homeostasis of lymphocytes and is essential in the negative selection and deletion of autoreactive cells (3,9,23). Recently, we reported that LPS protects primary B lymphocytes from both spontaneous and drug-induced apoptosis by preventing mitochondrial translocation of Bax, a proapoptotic protein of the Bcl2 family (45). It has been reported that Bax translocation could be blocked by Bcl-x L , the prosurvival protein of the Bcl2 family (13) whose expression could be enhanced by nuclear factor B (NF-B) activation (8).…”

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confidence: 99%

Lipopolysaccharide fromSalmonella entericaActivates NF-κB through both Classical and Alternative Pathways in Primary B Lymphocytes

2007

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Lipopolysaccharides (LPS) are potent polyclonal B-lymphocyte activators. Recently, we have shown that LPS inhibits both spontaneous and drug-induced apoptosis in mature B lymphocytes, through cytosolic retention of Bax, a proapoptotic protein of the Bcl-2 family, by preventing its translocation to mitochondria. Research within the last few years has revealed that members of the NF-B transcription factor regulate cell viability by activating genes involved in mitochondrion-dependent apoptosis. In this report, we examined the effect of sustained LPS stimulation on cytosolic and nuclear proteins of the IB/NF-B family to determine which NF-B pathway, canonical (classical) or noncanonical (alternative), is activated by this agent in mature B cells. Immunoblotting analyses showed that LPS induced a time-dependent degradation of the NF-B inhibitors IB␤ and IB (preferentially to isoform IB␣), via IB kinase ␤. In addition, we observed that LPS triggered the processing of NF-B p105 to p50 and that of NF-B p100 to p52 in parallel with nuclear translocation of active p50 and p52, as NF-Bp50/RelA and NF-Bp52/RelB heterodimers, respectively. These results suggest that sustained stimulation with LPS can activate NF-B through both classical and alternative pathways.

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Lipopolysaccharide Protects Primary B Lymphocytes from Apoptosis by Preventing Mitochondrial Dysfunction and Bax Translocation to Mitochondria

Cited by 19 publications

References 47 publications

Deletion of Exon I of SMAD7 in Mice Results in Altered B Cell Responses

Deletion of Exon I of SMAD7 in Mice Results in Altered B Cell Responses

Heat Shock Protein 60, via MyD88 Innate Signaling, Protects B Cells from Apoptosis, Spontaneous and Induced

Lipopolysaccharide fromSalmonella entericaActivates NF-κB through both Classical and Alternative Pathways in Primary B Lymphocytes

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