Activated B cells suppress T-cell function through metabolic competition.

Area of Science:

• Immunology
• Cancer Biology
• Metabolic Research

Background:

• B cells are crucial regulators of immune responses.
• Activated B cells can induce immunosuppression, but the underlying mechanisms remain unclear.

Purpose of the Study:

• To investigate the role of activated B cell metabolic activity in T-cell suppression.
• To explore the impact of B cell metabolism on anti-tumor immunity.

Main Methods:

• In vitro experiments and analysis of clinical samples.
• Utilized mass cytometry and single-cell RNA sequencing.

Main Results:

• Activated B cells exhibit an immunoregulatory phenotype, suppressing T cells via metabolic competition.
• B cells increase oxidative phosphorylation (OXPHOS), inducing T-cell hypoxia, and increase glycolysis, leading to glucose deprivation and lactic acid production.
• This metabolic reprogramming inhibits the mammalian target of rapamycin (mTOR) pathway in T cells, suppressing their cytokine production and proliferation.
• Tumor-associated B cells in melanoma patients display high glycolytic and OXPHOS activity, correlating with poor response to immune checkpoint blockade therapy.

Conclusions:

• Revealed the immunomodulatory effects of activated B cell metabolism on T-cell responses.
• Highlighted the potential role of B cell immunometabolism in suppressing anti-tumor immunity.
• Provided novel insights into immunometabolism with implications for cancer immunotherapy.