Thursday, April 23, 2026

NEW STUDY: B Cells Tht Fight Infections May Also Boost Muscle Performance During Exercise >> a chemical that helps initiate the pathway supplying muscles with the energy they need to work harder.

In this study, the researchers focused on the role of B cells in facilitating exercise capacity. The researchers compared normal mice to groups of mice whose B cells were eliminated either via genetic modification or with an antibody that temporarily removes the cells. They also modified mice so that only their B cells were unable to produce the signaling growth factor protein TGF-β1.

Physical activity is also known to influence the immune system. For instance, exercise causes muscles to release a signaling molecule called IL-6—a pro-inflammatory mediator and a key regulator of immune responses—which acts on immune cells within muscle tissue. What remains uncertain, however, is whether the immune system, particularly B cells, can in turn influence exercise capacity.

B cells that fight infections may also boost muscle performance during exercise

by Sanjukta Mondal, Medical Xpress

edited by Gaby Clark, reviewed by Robert Egan

B cells are white blood cells that form a core part of the body's adaptive immune system, enabling it to recognize specific infections, remember them, and mount a targeted response by producing antibodies.

A recent study published in Cell has found that these same cells might have a role to play in maintaining high exercise performance.

The team compared exercise performance, such as treadmill endurance and grip strength, in normal mice with those modified to lack B cells and found that mice without B cells performed much worse in these tests.

This discovery points to a mechanism that goes beyond immune function.
B cells appear to drive an immune-independent liver-muscle metabolic signaling, which starts with releasing a protein that travels to the liver, where it is converted into a chemical that helps initiate the pathway supplying muscles with the energy they need to work harder.

Role beyond immunity

Treatments that target a protein called CD20 on the surface of B cells have proven effective against specific cancers. The trade-off is that they do not distinguish between harmful and healthy cells and end up removing both. Even though B cells are well known for their role in fighting infections, it is still unclear whether they have functions beyond immunity and knowing those is essential for supporting people undergoing treatments that deplete B cells.

B cell deficiency alters Glu metabolism in multiple tissues. Credit: Cell (2026). DOI: 10.1016/j.cell.2026.03.039

B cell deficiency limits exercise capacity by remodeling liver glutamate metabolism

Youxiang Mao^1,4 ∙ Ziyan Xia^1,4 ∙ Xu Pan^1,2,3,4 ∙ Wenjun Xia¹ ∙ Peng Jiang^1,5 Send email to pengjiang@tsinghua.edu.cn

Supports open access

Highlights

•

B cell deficiency limits exercise performance and skeletal muscle function

•

B cells sustain peripheral glutamate levels to enhance exercise capacity

•

B cell-derived TGF-β1 reprograms hepatic glutamine catabolism and antiport

•

Glutamate activates functional signaling and metabolism in skeletal muscle

Summary

B cells are an essential component of humoral immunity, and B cell depletion therapies have clinically succeeded in eliminating cancerous B cells and treating autoimmune diseases.

Here, we report an immune-independent function of B cells that spatially and metabolically drives exercise capacity.

During exercise, B cell deficiency reduces transforming growth factor (TGF)-β1 production, which alters hepatic glutamate metabolism and decreases blood and muscle glutamate.
Mechanistically, B cell-derived TGF-β1 transcriptionally upregulates hepatic glutaminase 2 (GLS2) and solute carrier family 7 member 5 (SLC7A5) expression, increasing glutamine catabolism and thus glutamate production in the liver.
The resulting increase in glutamate fosters skeletal muscle calcium oscillations, calmodulin-dependent protein kinase (CaMK) kinase activity, and mitochondrial biogenesis, thereby improving exercise performance.

Thus, we identify a metabolite-driven liver-muscle connection that regulates exercise capacity, linking B cell function to skeletal muscle calcium signaling via alteration of hepatic glutamate metabolism.

By comparing normal and modified mice, researchers mapped a three-step communication chain through which B cells enhance exercise capacity. First, B cells release the protein TGF-β1 into the bloodstream. This signal reaches the liver, prompting it to convert glutamine into glutamate. The glutamate then enters the blood and travels to the muscles, where it boosts calcium signaling and improves mitochondrial function, which is needed to provide muscles with the energy they need to work harder.

B cells have traditionally been associated with fighting infections, with little connection to muscle performance, and these findings highlight a lesser-known role of these immune cells. The authors emphasize that their findings are based on mouse models. Human clinical studies are still needed to confirm whether these metabolic links hold true in people and whether they could be harnessed to improve exercise performance or muscle health.

Current Issue