Targeting immune cell metabolism to counteract unwanted antibody responses

Rebecca Cornelis, a postdoctoral researcher at Sanquin, is investigating strategies to counteract unwanted antibody responses, which occur in autoimmune diseases, blood transfusions, and biological drug treatments. Her approach focuses on disabling B cells, the antibody-producing cells. When B cells mature, they develop into long-lived plasma cells, which operate at high capacity and reside in the bone marrow, where they are difficult to target with therapeutics. These cells can produce an astonishing 1,000 antibodies per second.

Rebecca aims to target precursor forms of these cells, which are circulating in the bloodstream, and therefore more accessible to medication. During their development into antibody-producing factories, B cells undergo a significant metabolic shift. "To sustain the production of such a high volume of antibodies, their metabolism must be exceptionally active," Rebecca explains. "Think of it like a bodybuilder relying on protein shakes." Therefore, she seeks to disrupt the energy management of these developing B cells.

A significant challenge in this research is the limited number of B cells in the blood, often rendering conventional research methods ineffective. To overcome this, Rebecca employs an innovative technique: she fixes the B cells, creates pores in their cell membranes, and then analyzes the proteins that are crucial for their metabolism. These proteins represent potential targets for therapeutic intervention. To identify these proteins, she utilizes a comprehensive panel of antibodies, specifically targeting known metabolic proteins, including glucose transporters. Thanks to funding from the Sanquin Research Fund, Rebecca is able to acquire this specialized antibody panel.

For her research, she uses blood samples collected from individuals at specific time points following COVID-19 vaccination. The vaccination activates B cells, stimulating their differentiation into antibody-producing cells. Additionally, to replicate the antibody response in the laboratory, Rebecca isolates B cells from donor blood and stimulates them with antigens such as the SARS-CoV-2 spike protein.