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Harnessing B cells could fight cancer or autoimmune diseases by targeting mitochondrial metabolism

New research finds a crucial role for Thioredoxin protein in regulatory B cells control of the immune system

17 April 2024
Two children in a hospital playing together while receiving cancer treatment

A type of white cells called regulatory B cells could be harnessed to fight cancers and to treat autoimmune diseases by either increasing or decreasing their function, as indicated by a new research.

In a new study published in Nature Immunology researchers from UCL, in collaboration with researchers from the University of Birmingham and the University of Surrey have found that regulatory B cells which are essential for regulating the human immune system rely on a protein called Thioredoxin (Trx) for proper function.

Through study of samples of B cells taken from healthy donors and patients with an autoimmune condition called Lupus (SLE), the teams were able to identify how Trx is required for the immune suppressive functions of regulatory B cells, and represents a potential therapeutic target for autoimmune diseases.

In addition, the same process of regulating Trx to control B cell function could help treat cancers through inhibiting regulatory B cell function.

Maintaining a balance between different B cell types is crucial for overall health

Professor Claudio Mauro

Claudia Mauri, Professor of Immunology at UCL and leader of the study said:

“B cells are a vital part of the immune system and have long been considered a potential avenue for autoimmune and cancer treatment. They are also versatile, and can be manipulated to differentiate in a number of different types including regulatory B cells.

“Our team investigated the energy requirements of various B cell populations and discovered that Bregs depend on mitochondrial electron transport and produce moderate levels of reactive oxygen species (ROS). Unregulated ROS release can damage mitochondria, leading to cellular and tissue injury.”

“In our latest study, we have identified the metabolic demands of these important B cell subset, and the key protein Trx involved in maintaining metabolic balance so that they can help fight disease and pathogens in the body. Through our work with blood taken from lupus patients, we can also see how a deficiency in Trx resulting in the B-reg cells not working properly which is a feature of these patients.

“Crucially, we can also see that Trx supplementation can turn that around.”

Power imbalance

 

Regulatory B cells are reliant on a sweet spot of energy supplied by cellular power supply, called mitochondria; as well as a ‘sweet spot’ of reactive oxygen species (ROS) produced by the mitochondria, and problems with this balance leads to B cells becoming pro-inflammatory.

The study found that insufficient levels of the Trx protein in B-reg cells of SLE patients led to loss of function in the channel that feeds energy into cells from the mitochondria and as a result increased levels of ROS. Results from the analysis of lupus patients’ blood samples found that B-reg cells showed the tell-tale signs of incorrectly functioning mitochondria and increased ROS, alongside lower levels of the Trx protein.

Claudio Mauro, Professor of Metabolism and Inflammation in the Institute of Inflammation at the University of Birmingham co-author of the paper said:

“During an immune response, B cells play critical roles in fighting infections by producing antibodies, pro-inflammatory cytokines, and by supporting the development of other inflammatory immune cells. Concurrently, a subset of B cells known as regulatory B cells (Bregs) suppresses excessive inflammation that may arise from unresolved infections. Maintaining a balance between different B cell types is crucial for overall health.

“This studies further highlights how metabolism of immune cells is a target for potential novel therapies and we are working in this space with this and other projects to deliver impact for the people benefits in the near future.”

Notes for editors

  • For media enquiries please contact Tim Mayo, Press Office, University of Birmingham, tel: +44 (0)7815 607 157.

  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 8,000 international students from over 150 countries.

  • The University of Birmingham is a founding member of Birmingham Health Partners (BHP), a strategic alliance which transcends organisational boundaries to rapidly translate healthcare research findings into new diagnostics, drugs and devices for patients. Birmingham Health Partners is a strategic alliance between seven organisations who collaborate to bring healthcare innovations through to clinical application:
    • University of Birmingham
    • University Hospitals Birmingham NHS Foundation Trust
    • Birmingham Women's and Children's Hospitals NHS Foundation Trust
    • Aston University
    • The Royal Orthopaedic Hospital NHS Foundation Trust
    • Sandwell and West Birmingham Hospitals NHS Trust
    • West Midlands Academic Health Science Network
    • Birmingham and Solihull Mental Health NHS Foundation Trust

Featured staff

  • Professor Claudio Mauro

    Professor of Metabolism and Inflammation

    Trained biochemist and cellular biologist before approaching immunological questions, motivated by the recent 'renaissance' in the interest in metabolism in widespread fields of the basic and clinical science.

    Phone: +44 (0)121 371 7892
    Email: c.mauro@bham.ac.uk

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