Researchers Discover Explosive Immune Cells
BGU and Stanford researchers identify ruptoblasts, immune cells that erupt to fight infection and drive tissue rejection.
Researchers from Ben-Gurion University of the Negev (BGU) and Stanford University have discovered a completely unknown type of immune cell that protects the body by literally erupting. The newly identified cells, named ruptoblasts, rewrite our understanding of the immune system by showing that powerful defense mechanisms can evolve from outside the classical bloodline.
Their findings were published earlier this month in the journal Cell.
The collaborative research was led by Prof. Benyamin Rosental from BGU’s Shraga Segal Department of Microbiology, Immunology, and Genetics and the Center for Regenerative Medicine and Stem Cells, alongside Prof. Bo Wang of Stanford University’s Department of Bioengineering in the schools of Engineering and Medicine.
A Cellular Eruption
Textbooks teach that our immune defense relies entirely on white blood cells. However, looking at flatworms, the team discovered that ruptoblasts actually belong to a completely different family of glandular cells.
Instead of attacking targets through direct contact, ruptoblasts act like cellular grenades. When they sense a spike in a hormone called activin—which acts like a distress flare in the body—it sets off a rapid chain reaction. Within minutes, the cell floods with calcium, triggering an eruption.
This eruption releases a wave of powerful, broad-spectrum killing agents that instantly destroy everything within the immediate blast zone.
A Shield Against Infection and Rejection
The researchers proved that this dramatic eruption serves two vital protective roles:
- Clearing Bacteria: When the researchers infected the flatworms with dangerous bacteria, neighboring immune cells released the activin signal, detonating the ruptoblasts. The blast wave was incredibly effective at shattering the membranes of the invading microbes within moments.
- Driving Tissue Rejection: By fusing tissues from two different flatworms together, the team observed an "organ rejection" response. The clash caused a severe buildup of the activin signal, causing mass eruptions and tissue lesions. When the researchers genetically removed the ruptoblasts, the destructive rejection stopped entirely.
- Cross-Species Power: In lab tests, the chemical cocktail released by the exploding cells proved so potent that it could easily wipe out mammalian cells, including human cancerous kidney cells. This unexpected cross-species potency proves the cell's weapons are universal, offering a radically new template for scientists looking to engineer cellular therapies to target human tumors or drug-resistant bacteria.
Built-in Safety Latches
Because an uncontained cellular eruption could trigger a dangerous chain reaction, nature built in strict safety features. Crucially, if a ruptoblast is accidentally crushed or killed mechanically, it releases absolutely no toxins. The killing agents require a precise biochemical switch triggered only by activin to become lethal. This ensures that neighboring ruptoblasts caught in the crossfire do not accidentally explode, and the toxic footprint naturally breaks down within 15 minutes.
An Ancient Evolutionary Trick
While these exploding cells are absent in standard laboratory models like mice or fruit flies, genetic mapping revealed that they are present in a wide variety of ancient, primitive organisms, suggesting they have a very deep evolutionary history.
"These findings reveal a completely new strategy that directly links hormonal signals with explosive immune defense," the authors note. "It shows how diverse nature can be when inventing ways to fight off infection and could eventually inspire new ways to engineer cellular therapies to target bad bacteria or malfunctioning cells".
The study was co-authored by Chew Chai, Eliya Sultan, Souradeep R. Sarkar, Lihan Zhong, Dania Nanes Sarfati, Orly Gershoni-Yahalom, Christine Jacobs-Wagner, and Hawa Racine Thiam.
This work was supported by the Human Frontier Science Program (HFSP) (Grant No. RGY0085/2019), the National Institutes of Health (NIH) (Grant No. 1Workspace35GM138061), and the European Research Council (ERC) (Grant No. 948476).
