BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas‐mediated cell death

Acosta-Rodríguez, Eva V.; Craxton, Andrew; Hendricks, Deborah W.; Merino, Mariano Lisandro; Montes, Carolina L.; Clark, Edward A.; Gruppi, Adriana

doi:10.1002/eji.200636698

Cited by 37 publications

(38 citation statements)

References 42 publications

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“…An alternative explanation for the cooperation of LPS with BAFF in B cell maturation is that TLR4 signal could lead to the upregulation of BAFF-R, increasing BAFF responsiveness. Many groups have recently described that TLR4 and TLR9 signaling upregulate receptors for BAFF in mature B cells, increasing survival and activation events mediated by BAFF (32,33). Nonetheless, in our system, transitional B cells were not able to upregulate BAFF-R expression upon LPS stimulation (Fig.…”

Section: Discussionmentioning

confidence: 57%

TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor

Hayashi

Granato

Paiva

et al. 2010

The Journal of Immunology

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We have previously shown that TLR4 triggering promotes the generation of CD23+CD93+ transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23+ transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF. For both BAFF and LPS, functional maturation of the IgM+CD23+CD93+ cells was confirmed by their higher proliferative response to anti-CD40 plus IL-4 compared with IgM+CD23negCD93+ cells. BAFF-R-Fc–mediated neutralization experiments showed that TLR4-induced B cell maturation was independent of BAFF. Distinct from BAFF, maturation by LPS relied on the activation of canonical NF-κB pathway, and the two factors together had complementary effects, leading to higher numbers of IgM+CD23+CD93+ cells with their simultaneous addition. Importantly, BCR cross-linking abrogated the generation of CD23+ B cells by LPS or BAFF, indicating that signals mimicking central tolerance act on both systems. Addition of cyclosporin A reverted BCR-mediated inhibition, both for BAFF and LPS, suggesting similar regulation of signaling pathways by calcineurin. Finally, LPS-injected mice showed a rapid increase of mature B cells in the bone marrow, suggesting that TLR4 signaling may effectively stimulate B cell maturation in vivo, acting as an accessory stimulus in B cell development, complementary to the BAFF physiological pathway.

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Section: Discussionmentioning

confidence: 57%

TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor

Hayashi

Granato

Paiva

et al. 2010

The Journal of Immunology

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“…Activation of intracellular TLRs in B cells by immune complexes containing nucleic acids up-regulates expression of BAFF receptors, particularly TACI [47,49], and increases BCR-mediated signalling. In contrast, activation of B cells via TLR-4 up-regulates BAFF-R preferentially and renders the cells sensitive to Fas-mediated apoptosis [50]. The triad of TLRs, type I IFNs and BAFF creates an amplification loop that propagates production of IgG autoantibodies to nucleic acids in the absence of T cell help [49] (Fig.…”

Section: Functions Of Baff and Aprilmentioning

confidence: 99%

BAFF: a local and systemic target in autoimmune diseases

Moisini

Davidson

2009

Clinical and Experimental Immunology

156

141

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“…When the speed of cell division exceeds that of cell death, an increase in the number of live cells after stimulation should be detected. In the literature, activation-induced cell death is triggered by BCR or CD40 signaling alone (32,33). Although CpG does not regulate mouse splenic B cell death, LPS is able to suppress cell apoptosis (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, activation-induced cell death is triggered by BCR or CD40 signaling alone (32,33). Although CpG does not regulate mouse splenic B cell death, LPS is able to suppress cell apoptosis (33,34). TLR2 has been reported to mediate apoptosis in the human THP-1 monocytic cell line and in mouse microglia cells (35,36), but its role in B cell apoptosis remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

Huang¹,

Kang²,

Chen³

et al. 2012

The Journal of Immunology

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Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam3CSK4-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-βR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB–driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.

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BAFF and LPS cooperate to induce B cells to become susceptible to CD95/Fas‐mediated cell death

Cited by 37 publications

References 42 publications

TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor

TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor

BAFF: a local and systemic target in autoimmune diseases

Decoy Receptor 3 Suppresses TLR2-Mediated B Cell Activation by Targeting NF-κB

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