December 29, 2023

Glucose metabolism influences B cell function

Glucose metabolism influences the qualities of activated, mature B cells — white blood cells that are required for antibody-mediated immune responses, Vanderbilt researchers discovered.

B cells — white blood cells that are required for antibody-mediated immune responses — are activated and mature in structures called germinal centers located in lymphoid organs like lymph nodes and the spleen. The capacity of germinal centers to promote B cell affinity maturation (the process by which B cells generate antibodies of increasing affinity during an immune response) and memory are critical for the efficacy of many vaccines. 

It has been controversial and unclear if B cells in germinal centers have increased uptake of glucose and if glucose is important for germinal center function or the ultimate production of antibodies. To address these questions, Mark Boothby, MD, PhD, and colleagues eliminated the glucose transporter GLUT1 specifically in B cells in mature mice with a normal repertoire of preimmune B cells. 

They found that limiting glucose transport impaired germinal center B cell numbers, affinity maturation, and antibody output and concentration in sera. 

The researchers also explored whether other simple sugars could substitute for glucose. They were surprised to find that a combination of galactose and mannose supported normal antibody secretion under glucose-free conditions in vitro. 

The findings, reported Jan. 1 in The Journal of Immunology, demonstrate that germinal centers depend on normal glucose influx, especially to produce antibody-secreting plasma cells, but that they have unexpected metabolic flexibility. Understanding how specific metabolic pathways impact immune cell function could point to therapeutic targets for promoting immune responses or reducing autoimmune disease processes, the authors note. 

Shawna Brookens, PhD, and Sung Hoon Cho, PhD, are co-first authors of the study. Other authors include Yeeun Paik, Kaylor Meyer, Ariel Raybuck, Chloe Park, Dalton Greenwood, and Jeffrey Rathmell, PhD. The research was supported by the National Institutes of Health (grants R01AI149722, R01AI153167, R01DK105550).