B cell overexpression of FCRL5 and PD-1 is associated with low antibody titers in HCV infection

Ogega, Clinton O.; Skinner, Nicole; Flyak, Andrew I.; Clark, Kendal; Board, Nathan L; Björkman, Pamela J.; Crowe, James E.; Cox, Andrea L.; Ray, Stuart C.; Bailey, Justin R.

doi:10.1371/journal.ppat.1010179

Cited by 6 publications

(3 citation statements)

References 52 publications

(74 reference statements)

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“…A previous study demonstrated that FCRL5 exerts binary and compartment-specific influence on innatelike B-cell receptor signaling, and implied a specialized counterregulatory role for FCRL5 at the intersection of innate and adaptive immunity (Zhu et al, 2013). Ogega and Skinner (2022) observed that B cell overexpression of FCRL5 was associated with low antibody titers in HCV infection, and limited upregulation of FCEL5 could potentially generate higher titers of protective antibodies against HCV or other pathogens. In addition, in recent years, many studies have found that FCRL5 was associated with several diseases.…”

Section: Discussionmentioning

confidence: 98%

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B

Yang

Wang

et al. 2022

Front. Microbiol.

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Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB).Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined.Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093–3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067–6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856–0.935), 0.45 (AUC = 0.852, 95% CI = 0.802–0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703–0.826), respectively.Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.

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Section: Discussionmentioning

confidence: 98%

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B

Yang

Wang

et al. 2022

Front. Microbiol.

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“…The PD-1/PD-L1 pathway is involved in the regulation of humoral immunity in addition to cellular immune regulation [25]. B cells can be activated by recognizing APC cell antigenic peptides directly or by follicular helper T cells (Tfh cells) in combination with costimulatory molecules.…”

Section: Discussionmentioning

confidence: 99%

Modification and Immune Function of Porcine PD-1 and PD-L1 Interaction Epitope Peptides

Yue

Shi

Zhou

et al. 2023

Preprint

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Background The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway transmits the negative immunoregulatory signals, leading to immunosuppression. Blocking the PD-1/PD-L1 pathway with peptides or antibodies can reverse the function of exhausted T cells, which can be a reference for developing studies on treating viral immunosuppressive diseases. Therefore, this work was developed to analyze the immune function of epitope peptides interacting with porcine PD-1 and PD-L1.Results After optimization, the proliferation percentages of PD-L14QN-GF and PD-L14QN-AF on PBMCS were 45.33%±6.16% and 56.20%±4.94%, respectively, which were increased by 14.7% and 25.8%. The inhibition rates of PD-L14QN-AF on PRRSV and PD-1 were 56.1.8% and 74.8%, which were increased by 35.0% and 29.4% compared with PD-L14, respectively. The inhibition rates of PD-L14QN-GF on PRRSV and PD-1 were 43.8% and 65.3%, which were 22.7% and 20.4% higher than those of PD-L14, respectively. The expression levels of IL-2 and IFN-γ in the PD-L14QN-GF group were 2.1 times and 2.8 times higher than those in the PD-L14 group and 1.2 times and 1.5 times higher than those in the PD-L14QN-AF group, respectively. The protein secretion levels of IL-2 and IFN-γ in the PD-L14QN-GF group were 2.5 times and 1.7 times higher than those in the PD-L14 group and 1.5 times and 1.2 times higher than those in the PD-L14QN-AF group, respectively. Furthermore, the PD-L14QN-GF and PD-L14QN-AF exhibited better immune effects than PD-L14. At 14 days after immunization, the antibody-positive rate in the PD-L14QN-GF group reached 80%, which was 30% and 50% higher than that in the PD-L14 group and normal group, respectively. The antibody titer in the PD-L14QN-GF group was 1.5 and 2 times higher than that in the PD-L14 and the normal groups, respectively.Conclusion PD-L14QN-GF was proved to be of high potential to develop immune-enhancing adjuvant.

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“…Those atMBC mainly targeted on HBsAg, which was expressed on the hepatocyte surface. atMBC in HBV highly expressed the coinhibitory receptors PD-1 and FcRL5, showing incomplete signaling pathway and cytokine production, as well as weakened ability to differentiate into mature plasma cells (17,21,32,33). CD11c, a molecule reflecting cell exhaustion and inflammatoryhoming ability, along with transcription factor T-bet was expressed on HBV-specific B cells (34,35).…”

Section: Discussionmentioning

confidence: 99%

Characterization of intrahepatic B cells in acute-on-chronic liver failure

Zhao

Wang²,

Wang³

et al. 2022

Front. Immunol.

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Background and objectivesAcute on chronic liver failure (ACLF) is characterized by the immunologic dissonance during the prolonged pathogenic development. Both abnormal innate immune response and adaptive T-cell response have been reported in patients with ACLF; however, less is known regarding B cells in ACLF pathogenesis. Previous reports were only based on immunophenotyping of peripheral blood samples. Here, we aim to dissect liver-infiltrating B-cell subpopulation in ACLF.MethodsPaired liver perfusate and peripheral blood were freshly collected from healthy living donors and recipients during liver transplantation. Liver tissues were obtained from patients with ACLF, cirrhosis, and healthy controls. Flow cytometry was used to characterize the phenotypic and functional alterations in intrahepatic and circulating B-cell populations from ACLF, cirrhosis, and healthy controls. The expression of CD19+ and CD138+ on liver tissues was examined by immunohistochemistry staining.ResultsIn this study, we first deciphered the intrahepatic B cells subsets of patients with ACLF. We found that the ACLF liver harbored reduced fraction of naïve B cells and elevated percentage of CD27+CD21− activated memory B cells (AM), CD27−CD21− atypical memory B cells (atMBC), CD27+IgD−IgM+(IgM+ memory B cells), and CD27+CD38++ plasma cells than cirrhosis and healthy controls. Moreover, these B subpopulations demonstrated enhanced activation and altered effector functions. Specifically, the ACLF liver was abundant in atMBC expressing higher CD11c and lower CD80 molecule, which was significantly correlated to alanine aminotransferase and aspartate aminotransferase. In addition, we found that intrahepatic CD27+CD38++plasma cells were preferentially accumulated in ACLF, which expressed more CD273 (PD-L2) and secreted higher granzyme B and IL-10. Finally, the enriched hepatic plasma B cells were in positive association with disease severity indices including alkaline phosphatase and gamma-glutamyl transferase.ConclusionsIn this pilot study, we showed an intrahepatic B-cell landscape shaped by the ACLF liver environment, which was distinct from paired circulating B-cell subsets. The phenotypic and functional perturbation in atMBC and plasma cells highlighted the unique properties of infiltrating B cells during ACLF progression, thereby denoting the potential of B-cell intervention in ACLF therapy.

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B cell overexpression of FCRL5 and PD-1 is associated with low antibody titers in HCV infection

Cited by 6 publications

References 52 publications

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B

Modification and Immune Function of Porcine PD-1 and PD-L1 Interaction Epitope Peptides

Characterization of intrahepatic B cells in acute-on-chronic liver failure

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