Researchers at the University of Colorado Anschutz Medical Campus have uncovered a critical, previously underappreciated role for B cells in vaccine protection. Best known for producing antibodies, B cells also guide other immune cells, specifically CD8 T cells, teaching them how to mount lasting defenses after vaccination.
The study was recently published in The Journal of Clinical Investigation.
“Think of CD8 T cells as rookie firefighters,” said lead author Jared Klarquist, PhD, assistant research professor of immunology and microbiology at the University of Colorado School of Medicine. “B cells teach the class on pacing. Without them, the rookies rush in, fight hard, and quit. They don’t save anything for the next fire.”
The study found that in the absence of B cells, CD8 T cells became overly active too early, burning out quickly and failing to develop into memory cells that provide long-term protection. This discovery sheds light on why some people don’t build strong immunity after vaccination, especially those receiving treatments that deplete B cells.
For example, more than 350,000 people have been treated with ocrelizumab, a drug that depletes B cells, since its approval in 2017. It’s commonly used to manage conditions like multiple sclerosis, lupus and certain cancers but it may also weaken long-term vaccine effectiveness.
“These patients don’t just struggle to make antibodies,” said Klarquist. “Their CD8 T cells are also less effective because they’re missing crucial guidance from B cells.”
One of the key molecules involved in this immune training is called FOXO1. It keeps CD8 T cells in a “ready-to-learn” state. When B cells are absent, FOXO1 levels drop and the T cells fail to develop into long-lasting memory cells.
“Using the firefighter metaphor, vaccines are like a fire drill, meant to teach the immune system to know how to fight a real fire — an infection,” said Klarquist. “But without B cells, that lesson doesn’t stick.”
The findings could shape future vaccine strategies, especially for immunocompromised individuals. Researchers suggest options like timing vaccines around B cell-depleting treatments, adding ingredients that mimic B cell signals or enhancing the CD8 T cell memory-building process directly.
“We still strongly recommend patients receiving these powerful treatments get vaccinated — there’s clear evidence they still offer some protection. Our goal is to build on that foundation and find ways to make that protection stronger and longer lasting,” said Klarquist.
The team’s next step is identifying exactly how B cells communicate with T cells. One possibility involves signaling proteins called cytokines. Replicating or amplifying these signals might allow patients to build strong immunity even without functioning B cells.
This research not only deepens scientists understanding of how vaccines work but could transform how to approach vaccination in patients with immune challenges and potentially improve vaccine effectiveness for more people.
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