B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

Borhis, Gwenoline; Trovato, Maria; Chaoul, Nada; Ibrahim, Hany M.; Richard, Yolande

doi:10.3389/fimmu.2017.01338

Cited by 15 publications

(15 citation statements)

References 168 publications

(214 reference statements)

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“…BAFF excess has been frequently associated with expansion/survival of self/poly-reactive B-cells during GC reaction (45)(46)(47) and more recently at the immature-transitional stage in mice (45). Therefore, BAFF overproduction during early HIV/SIV infection might be beneficial to B-cells producing broadly neutralizing Abs against HIV, a substantial fraction of them bearing self-/polyreactive B-cell receptor (BCR) (48,49). However, recent studies failed to demonstrate a beneficial effect of BAFF overexpression in their development.…”

Section: Introductionmentioning

confidence: 99%

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection

et al. 2020

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Memory B-cell dysfunctions and inefficient antibody response suggest germinal center (GC) impairments during HIV/SIV infection with possible contribution of overproduced B-cell activating factor (BAFF). To address this question, we compared proportions and functions of various B-cell subsets and follicular helper T-cells (T FH) in untreated (Placebo) and BR3-Fc treated (Treated) SIV-infected macaques. From day 2 post-infection (dpi), Treated macaques received one weekly injection of BR3-Fc molecule, a soluble BAFF antagonist, for 4 weeks. Whereas, the kinetics of CD4 + T-cell loss and plasma viral loads were comparable in both groups, BAFF blockade delayed the peak of inflammatory cytokines (CXCL10, IFNα), impaired the renewal of plasmacytoid dendritic cells and fostered the decline of plasma CXCL13 titers after 14 dpi. In Treated macaques, proportions of total and naïve B-cells were reduced in blood and spleen whereas SIV-induced loss of marginal zone (MZ) B-cells was only accentuated in blood and terminal ileum. Proportions of spleen GC B-cells and T FH were similar in both groups, with CD8 + T-cells and rare Foxp3 + being present in spleen GC. Regardless of treatment, sorted T FH produced similar levels of IL21, CXCL13, and IFNγ but no IL2, IL4, or BAFF and exhibited similar capacities to support IgG production by autologous or heterologous B-cells. Consistently, most T FH were negative for BAFF-R and TACI. Higher proportions of resting and atypical (CD21 lo) memory B-cells were present in Treated macaques compared to Placebo. In both groups, we found higher levels of BAFF-R expression on MZ and resting memory B-cells but low levels on atypical memory B-cells. TACI was present on 20-30% of MZ, resting and atypical memory B-cells in Placebo macaques. BAFF blockade decreased TACI expression on these B-cell subsets as well as titers of SIV-specific and vaccine-specific antibodies arguing for BAFF being mandatory for plasma cell survival. Irrespective of treatment, GC B-cells expressed BAFF-R at low level and were negative for TACI. In addition to key information on spleen BAFF-R and TACI expression, our data argue for BAFF contributing to the GC reaction in terminal ileum but being dispensable for the generation of atypical memory B-cells and GC reaction in spleen during T-dependent response against SIV.

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Section: Introductionmentioning

confidence: 99%

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection

et al. 2020

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“…BAFF is a key factor for the survival of B cells and homeostasis (6). BAFF excess might contribute to the abnormal rescue of self-reactive and might be a key role in B-cell dysregulation (7).…”

Section: Introductionmentioning

confidence: 99%

B-Cell Activating Factor Predicts Acute Rejection Risk in Kidney Transplant Recipients: A 6-Month Follow-Up Study

et al. 2019

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B cell activating factor (BAFF) belonging to TNF family is a cytokine that enhances B-cell proliferation and differentiation. Recently, It has been suggested that BAFF might be a potential therapeutic target for treating autoimmune disease. However, the relationship between BAFF and allograft rejection is controversial, and the clinical significance of BAFF in predicting allograft rejection need to be further explored. We conducted 6-month follow-up study to confirm the hypothesis that BAFF might be a risk factor for predicting acute rejection in kidney transplant recipients. At the end of the study, a total of 155 kidney transplant recipients were recruited from October 2015 to October 2017, and classified into acute rejection group ( n = 34) and stable renal function group ( n = 121) according to their clinical course. We demonstrate that the serum BAFF levels when acute rejection occurred was significantly higher than that in the stable renal function group (2426.19 ± 892.19 vs. 988.17 ± 485.63 pg/mL, P < 0.05). BAFF expression was significantly enhanced in the membrane and cytoplasm of renal tubule epithelial cells in the transplant kidney tissue with acute rejection, and a positive correlation between BAFF and C4d expression was also observed ( r = 0.880, P = 0.001). ROC analyses highlight the superiority of serum BAFF level before transplant over those on other post-transplant days in prediction of acute rejection episodes. The sensitivity, specificity and AUC (area under curve) were 83.3, 89.5, and 0.886%, respectively. Kaplan-Meier survival analysis showed that recipients with higher pretransplant BAFF levels had higher acute rejection incidence ( P = 0.003). In conclusion, we have identified that BAFF levels are associated with the acute rejection and could be a promising biomarker to predict kidney transplant rejection risks.

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“…Age, gender, Rose-Bengal test results, transaminase levels, and other laboratory parameters were not significantly different between the patients with and without complication(s) ( Table 2). The symptomatic periods were not different between the patients with and without complications [30(20-60) vs. 25 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), p=0.07]. BAFF and APRIL levels were also indiscriminative between the patients, as shown in Table 2.…”

Section: Resultsmentioning

confidence: 92%

“…Also, BAFF deficiency was shown to result in increased mortality rates related to West Nile virus infection and decreased virus-specific IgG and neutralizing antibody responses (18) . However overexpression of BAFF has been associated with progression of infectious diseases as HIV/SIV (19) . Excessive overexpression of BAFF may contribute to the inhibition of selfreactive B-cells during the B-cell development and impair memory B-cell generation and functions.…”

Section: Discussionmentioning

confidence: 99%

Increased BAFF Levels in Children with Acute Brucellosis

Erdeniz¹,

Cevik²

2020

Trends in Pediatrics

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Objective: Brucellosis is a chronic infectious disease. We aimed to show the association of serum 'A PRoliferation-Inducing Ligand (APRIL) (TNFSF13A)' and 'B-cell Activating Factor (BAFF)' levels belonging to the tumor necrosis factor family in children with acute brucellosis. Methods: Fifty children with acute brucellosis and 35 healthy controls who were admitted during a two-year period between 2018 and 2020 were prospectively included in the study. All patients and healthy children were tested for complete blood counts, C-reactive protein, BAFF, and APRIL levels, and erythrocyte sedimentation rate. Results: The mean age of 50 patients with acute brucellosis was 10.2±3.6 years, and 37 (74%) of them was male. BAFF levels were significantly higher in children with acute brucellosis than the control group (548.6±253.4 vs. 280.5±83.6, p<0.001). In addition to APRIL levels, other laboratory tests were not statistically significantly different between the patients and control group. Neither BAFF and APRIL, nor age, gender, Rose-Bengal test results, transaminase levels, and other laboratory parameters were significantly different between the patients with and without any complication(s). ROC analysis showed that BAFF values above 330 pg/mL were 78% sensitive and 72% specific for the detection of acute brucellosis in children (area under curve:0.864, p<0.001, CI:0.787-0.941). Conclusion: BAFF levels were significantly elevated in children with acute brucellosis. BAFF levels above 330 pg/mL were 78% sensitive and 72% specific for the detection of the disease, but BAFF could not discriminate between patients with and without complications. APRIL, which has relatively similar effects, is not associated with acute pediatric brucellosis.

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B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

Cited by 15 publications

References 168 publications

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection

Impact of BAFF Blockade on Inflammation, Germinal Center Reaction and Effector B-Cells During Acute SIV Infection

B-Cell Activating Factor Predicts Acute Rejection Risk in Kidney Transplant Recipients: A 6-Month Follow-Up Study

Increased BAFF Levels in Children with Acute Brucellosis

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