Inhibition of B‐cell activation and antibody production by triggering inhibitory signals via the <scp>PD</scp>‐1/<scp>PD</scp>‐ligand pathway

Buermann, Anna; Römermann, Dorothee; Baars, Wiebke; Hundrieser, J.; Klempnauer, Jürgen; Schwinzer, Reinhard

doi:10.1111/xen.12261

Cited by 25 publications

(27 citation statements)

References 41 publications

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“…Preferential PD-1 expression on differentiated and activated B cells in blood and CSF. Programmed death-1 (PD-1) is a surface regulatory "check point" molecule identified prominently on T follicular helper cells and, less frequently, on B cells, NK cells, NKT cells, and other myeloid-derived cells (18). PD-1 was expressed on a minority of circulating B cells but significantly more commonly on B cells in the CSF (Fig.…”

Section: Resultsmentioning

confidence: 99%

B Cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis

et al. 2020

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Activated B cells modulate infection by differentiating into pathogen-specific antibody-producing effector plasmablasts/plasma cells, memory cells, and immune regulatory B cells. In this context, the B cell phenotypes that infiltrate the central nervous system during human immunodeficiency virus (HIV) and cryptococcal meningitis coinfection are ill defined. We characterized clinical parameters, mortality, and B cell phenotypes in blood and cerebrospinal fluid (CSF) by flow cytometry in HIV-infected adults with cryptococcal (n = 31) and noncryptococcal (n = 12) meningitis and in heathy control subjects with neither infection (n = 10). Activation of circulating B cells (CD21low) was significantly higher in the blood of subjects with HIV infection than in that of healthy controls and greater yet in matched CSF B cells (P < 0.001). Among B cell subsets, elevated frequencies of memory and plasmablasts/plasma cells most clearly distinguished the CSF from blood compartments. With cryptococcal meningitis, lower frequencies of expression of the regulatory protein programmed death-1 (PD-1) on plasmablasts/plasma cells in blood (median, 7%) at presentation were associated with significantly decreased 28-day survival (29% [4/14 subjects]), whereas higher PD-1 expression (median, 46%) characterized subjects with higher survival (88% [14/16 subjects]). With HIV infection, B cell differentiation and regulatory markers are discrete elements of the circulating and CSF compartments with clinical implications for cryptococcal disease outcome, potentially due to their effects on the fungus and other local immune cells.

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Section: Resultsmentioning

confidence: 99%

B Cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis

et al. 2020

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“…PD‐1 is thought to be involved in the induction of anergy and exhaustion in CD8 + T cells . Furthermore, we and others have shown that PD‐L1‐mediated triggering of PD‐1 on B cells decreases activation and antibody production . The diversity of cell types and functions that are modulated by PD‐1/PD‐L1 is in line with the view of this receptor‐ligand pair as important regulator of immune checkpoints.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the physiological role of PD‐1/PD‐L1 and the observations in allotransplantation, transgenic expression of human PD‐L1 on porcine cells is promising to protect porcine tissue from human immune responses. As proof‐of‐principle, we and others have shown that porcine cells over‐expressing human PD‐L1 are indeed weak stimulators of immune responses in vitro and also in a pig‐to‐rat cell transplantation model in vivo . The usefulness of this concept has not yet been investigated in transgenic pigs.…”

Section: Introductionmentioning

confidence: 99%

Pigs expressing the human inhibitory ligand PD‐L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties

Buermann

Petkov

Petersen

et al. 2018

Xenotransplantation

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“…The resurgence of xenotransplantation is now obvious [9,10,106], with prolonged survival of cellular and solid organ xenografts (Figure 2) associated with the administration of newer costimulation blockade agents [107,108] and access to genetically-engineered pigs. Our increasing knowledge of the pig genome [109] will almost certainly lead to further genetic manipulations.…”

Section: Resultsmentioning

confidence: 99%

Xenotransplantation

Ekser

Li²,

Cooper³

2017

Current Opinion in Organ Transplantation

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Purpose of review To review the progress in the field of xenotransplantation with special attention to most recent encouraging findings which will eventually bring xenotransplantation to the clinic in the near future. Recent findings Starting from early 2000, with the introduction of Gal-knockout pigs, prolonged survival especially in heart and kidney xenotransplantation was recorded. However, remaining antibody barriers to nonGal antigens continue to be the hurdle to overcome. The production of genetically-engineered pigs was difficult requiring prolonged time. However, advances in gene editing, such as zinc finger nucleases, transcription activator-like effector nucleases, and most recently CRISPR technology made the production of genetically-engineered pigs easier and available to more researchers. Today, the survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet xenotransplantation reached >900 days, >400 days, and >600 day, respectively. The availability of multiple-gene pigs (5 or 6 genetic modifications) and/or newer costimulation blockade agents significantly contributed to this success. Now, the field is getting ready for clinical trials with an international consensus. Summary Clinical trials in cellular or solid organ xenotransplantation are getting closer with convincing preclinical data from many centers. The next decade will show us new achievements and additional barriers in clinical xenotransplantation.

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Inhibition of B‐cell activation and antibody production by triggering inhibitory signals via the PD‐1/PD‐ligand pathway

Abstract: Enhancing inhibitory signals may be part of future protocols to better control humoral immunity to allo- and xenografts.

Cited by 25 publications

References 41 publications

B Cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis

B Cell Compartmentalization in Blood and Cerebrospinal Fluid of HIV-Infected Ugandans with Cryptococcal Meningitis

Pigs expressing the human inhibitory ligand PD‐L1 (CD 274) provide a new source of xenogeneic cells and tissues with low immunogenic properties

Xenotransplantation

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