Abstract
Background and AimsPatients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.MethodsChanges in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.ResultsThe proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.ConclusionsB cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines.
Highlights
Cirrhosis is the end stage of all liver diseases and is the 14th most common cause of death worldwide [1]
We found that B cells from decompensated liver cirrhosis (D-LC) patients showed reductions in Oxidative phosphorylation (OXPHOS) and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway
Cirrhotic patients are susceptible to bacterial infections, which may lead to acute decompensation (AD) and acute-on-chronic liver failure (ACLF), both of which are associated with high short-term mortality [2, 3]
Summary
Cirrhosis is the end stage of all liver diseases and is the 14th most common cause of death worldwide [1]. Cirrhotic patients are susceptible to bacterial infections, which may lead to acute decompensation (AD) and acute-on-chronic liver failure (ACLF), both of which are associated with high short-term mortality [2, 3]. The immune dysfunction associated with cirrhosis starts with the onset of chronic liver inflammation, becomes worse with the development of portal hypertension, further deteriorates due to gut bacterial translocation, and culminates in immune paralysis in ACLF. Patients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism
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