FAU team identifies effect of GLUT1 deficiency on B-lymphocytes

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Dr. Katharina Pracht (image: S. Krikrava/Uniklinikum Erlangen)

How a protein influences the functioning of the immune system

Cells with certain pre-determined tasks are essential to the human immune system, allowing it to recognize and render pathogens harmless. Changes can lead to the immune system providing us with less protection from disease. A research team from the Department of Molecular Immunology (head: Prof. Dr. Hans-Martin Jäck) at Uniklinikum Erlangen led by Dr. Katharina Pracht has now discovered that a protein named glucose transporter 1 (GLUT1) is of major significance for the functioning of certain cells within the immune system, the antibody-secreting B lymphocytes. The researchers recently published their findings in the journal Cell Reports.

B-lymphocytes are cells in the acquired immune system that are generated upon contact with a pathogen or after vaccination with antibody-secreting plasma cells. Antibodies recognize the pathogen the next time they come into contact with it and alarm other cells that then eradicate the pathogen. GLUT1 ensures that the sugar molecule glucose penetrates the B-lymphocyte cells and provides the cells with energy. B-lymphocytes require significant amounts of energy to produce antibodies. If the cells lack GLUT1, less glucose enters the cells and the B-lymphocytes are unable to function as effectively.

The FAU team used a pre-clinical model in which GLUT1 is only switched off in B lymphocytes in order to investigate the influence of a GLUT1 deficiency on B lymphocytes. As a result, the B lymphocytes were slower to react and produced fewer protective antibodies after a vaccine. One of the reasons for the reduced activity of the B lymphocytes is that they were unable to reproduce as effectively due to the lack of sugar entering the cells with the help of GLUT1, and struggled to develop into antibody-secreting cells. As well as the reduced energy supply caused by a GLUT1 deficiency, the team led by Dr. Pracht discovered that the B lymphocytes were also missing certain components for their growth due to a poorer metabolism. The FAU study therefore demonstrates that a lack of glucose in B lymphocytes also influences signaling pathways and processes that are not exclusively geared to gaining energy. In the long-term, this can lead to an alteration in the activity of B lymphocytes and antibodies.

The results of the study do not only contribute to a fundamental understanding of the acquired immune system, they are also of significance for people with the rare GLUT1 deficiency syndrome. This disease is caused by mutations in the GLUT1 gene sequence and leads to severe neurological complaints from childhood. It is not possible to come to any conclusions at the current time concerning the influence of the GLUT1 mutation on the long-term effect of vaccinations or on the development of autoimmune diseases such as rheumatoid arthritis that often only become apparent with age. However, it is recommended regularly checking the vaccination status of patients with GLUT1 deficiency syndrome and adjusting vaccination intervals if necessary in order to ensure protection against dangerous pathogens.

Further information:

Dr. Katharina Pracht

Department of Molecular Immunology at the Department of Medicine 3

Phone: + 49 9131 85 39339