The complexity of the BAFF TNF-family members: Implications for autoimmunity

Lahiri, Ayan; Pochard, Pierre; Pottier, Laëtitia Le; Tobón, Gabriel J.; Bendaoud, Boutahar; Youinou, Pierre; Pers, Jacques‐Olivier

doi:10.1016/j.jaut.2012.05.009

Cited by 46 publications

(29 citation statements)

References 112 publications

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“…However, caution should be put in interpreting the clinical associations of BAFF serum levels in RA and autoimmune diseases in general. In fact, BAFF family members exist in several different forms depending on protein structure, splice variants, glycosylation, and cleavage, each with possible specific biological activities [94], and BAFF quantification based on ELISA commercial kits was found to be largely inaccurate [95]. …”

Section: B Cells As Biomarkersmentioning

confidence: 99%

“…Although BAFF levels were not found to be associated with clinical response, a recent study analyzing 138 seropositive RA patients indicates BAFF levels >1011 pg/ml as an independent predictor of a good EULAR response in this subgroup of patients [121]. Again, contrasting results might depend on the different clinical features of the patients' population being analyzed, as well as on the inaccuracy of BAFF serum level measurements due to the biological complexity of this cytokine [94, 95]. …”

Section: B Cells As Biomarkersmentioning

confidence: 99%

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B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Bugatti

Vitolo

Caporali

et al. 2014

BioMed Research International

137

113

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The therapeutic benefit of depleting B cells in rheumatoid arthritis (RA) has refocused attention on B cells with increasing awareness on their role in autoimmunity and their function beyond autoantibody production. The rapid increase in our comprehension of B-cell pathobiology is progressively opening novel perspectives in the area of B cell-targeted therapies with the expectation to define more specific approaches able to preserve the homeostasis of the humoral response while disrupting the pathogenic components. In parallel, B-cell activity in RA is starting to be explored in its clinical value, in search of novel biomarkers embedded in the pathogenic process that could help classifying the disease and predicting its heterogeneous outcome beyond inflammation dynamics. In this review, we summarize current knowledge on the multiple roles that B cells play in several aspects of RA. We also analyze their distribution and potential function in different anatomic compartments with specific reference to the main sites in which the disease may be sustained and exert its detrimental effects: the systemic circulation, synovium, bone marrow, and draining lymph nodes. We also highlight novel data encouraging further research in the field of biomarkers related to B cells and their regulatory factors.

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Section: B Cells As Biomarkersmentioning

confidence: 99%

Section: B Cells As Biomarkersmentioning

confidence: 99%

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Bugatti

Vitolo

Caporali

et al. 2014

BioMed Research International

137

113

View full text Add to dashboard Cite

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“…Polymorphism rs9514828 (−871 C>T) in the promoter region of the BAFF gene has been associated with high levels of serum BAFF and familial CLL [3] and NHL risk [13]. A new mutation in the BAFF-R gene rs61756766 (His159Tyr) was determined in tumor and germline tissues from a subset of NHL patients [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Association of variants in BAFF (rs9514828 and rs1041569) and BAFF-R (rs61756766) genes with the risk of chronic lymphocytic leukemia

et al. 2016

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The B-cell activator factor (BAFF)/BAFF receptor (BAFF-R) axis seems to play an important role in the development and progression of chronic lymphocytic leukemia (CLL). Here, we investigated the association of eight single nucleotide polymorphisms (SNPs) in the BAFF (TNFSF13B) and BAFF-R (TNFRSF13C) genes with risk of sporadic CLL in a group of 439 CLL patients and 477 controls. We also examined the correlation between selected SNPs and CLL clinical parameters as well as BAFF plasma levels and intracellular BAFF expression. Our results point to a possible association between the rs9514828 (CT vs. CC + TT; OR = 0.74; CI 95 % = 0.57; 0.97; p = 0.022) and rs1041569 (AT vs. AA + TT; OR = 0.72; CI 95 % = 0.54; 0.95; p = 0.021) of BAFF gene and rs61756766 (CC vs. CT; OR = 2.03; CI 95 % = 1.03; 3.99; p = 0.03) of BAFF-R gene and CLL risk. Additionally, we observed that homozygotes rs1041569 AA and TT had a slightly higher risk (HR = 1.12) for the need of treatment in comparison to AT heterozygotes. In conclusion, our results indicate that SNPs in BAFF and BAFF-R genes may be considered as potential CLL risk factors.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-5182-z) contains supplementary material, which is available to authorized users.

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“…Excessive endogenous and transgenic BAFF in mice prolongs the life span and increases the population of peripheral B lymphocytes, resulting in elevated secretion of superfluous autoantibodies [6]. BAFF is likely involved in the pathogenesis of a number of autoimmune diseases [7]. BAFF overexpression has been reportedly associated with the breakdown of B cell tolerance and autoantibody production.…”

Section: Introductionmentioning

confidence: 99%

BAFF inhibits autophagy promoting cell proliferation and survival by activating Ca2+-CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells

Dong

Qin

et al. 2019

Cellular Signalling

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B cell activating factor from the TNF family (BAFF) is implicated in not only the physiology of normal B cells, but also the pathophysiology of aggressive B cells related to malignant and autoimmune diseases. Autophagy plays a crucial role in balancing the beneficial and detrimental effects of immunity and inflammation. However, little is known about whether and how excessive BAFF mediates autophagy contributing to B-cell proliferation and survival. Here, we show that excessive human soluble BAFF (hsBAFF) inhibited autophagy with a concomitant reduction of LC3-II in normal and B-lymphoid (Raji) cells. Knockdown of LC3 not only potentiated hsBAFF inhibition of autophagy, but also attenuated hsBAFF activation of Akt/mTOR pathway, thereby diminishing hsBAFF-induced B-cell proliferation/viability. Further, we found that hsBAFF inhibition of autophagy was Akt/mTOR-dependent. This is supported by the findings that hsBAFF increased mTORC1-mediated phosphorylation of ULK1 (Ser757); Akt inhibitor X, mTORC1 inhibitor rapamycin, mTORC1/2 inhibitor PP242, expression of dominant negative Akt, or knockdown of mTOR attenuated hsBAFF-induced phosphorylation of ULK1, decrease of LC3-II level, and increase of cell proliferation/viability. Chelating intracellular free Ca2+ ([Ca2+]i) with BAPTA/AM or preventing [Ca2+]i elevation using EGTA or 2-APB profoundly blocked hsBAFF-induced activation of Akt/mTOR, phosphorylation of ULK1 and decrease of LC3-II, as well as increase of cell proliferation/viability. Similar effects were observed in the cells where CaMKII was inhibited by KN93 or knocked down by CaMKII shRNA. Collectively, these results indicate that hsBAFF inhibits autophagy promoting cell proliferation and survival through activating Ca2+-CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells. Our findings suggest that manipulation of intracellular Ca2+ level or CaMKII, Akt, or mTOR activity to promote autophagy may be exploited for prevention of excessive BAFF-induced aggressive B lymphocyte disorders and autoimmune diseases.

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The complexity of the BAFF TNF-family members: Implications for autoimmunity

Cited by 46 publications

References 112 publications

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

B Cells in Rheumatoid Arthritis: From Pathogenic Players to Disease Biomarkers

Association of variants in BAFF (rs9514828 and rs1041569) and BAFF-R (rs61756766) genes with the risk of chronic lymphocytic leukemia

BAFF inhibits autophagy promoting cell proliferation and survival by activating Ca2+-CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells

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