Antibody feedback reshapes B cell selection during immune response

 A collaborative study published in Immunity from the Batista Lab and Liu Lab at the Ragon Institute, together with the Schief Lab at Scripps Research Institute, has uncovered a previously unrecognized mechanism that shapes how immune cells are selected during an immune response.

When the immune system encounters a pathogen or vaccine, B cells that recognize the threat gather in structures called germinal centers. There, they undergo rounds of mutation and selection that produce increasingly effective antibodies-a process scientists have long understood as purely competitive-with the strongest-binding B cells winning out over weaker ones.

The new findings reveal an additional layer of control. Using mouse models, the team found B cells that bound the target most strongly actually spent less time in germinal centers than weaker-binding cells. And while B cells of similar strength could coexist without affecting each other, stronger-binding cells actively suppressed weaker ones targeting the same site.

"When we started examining this response, it became clear that the effect was highly localized, anatomically," first author and Batista Lab research scientist Yu Yan, PhD, said. "We were able to identify cells in and around the germinal centers producing antibodies creating a hyperlocal feedback loop."

The germinal center's own output acts as a "brake" that limits further selection against that particular target and appears to serve an important purpose.

"Antibody binding only needs to be so high for protection. Eventually, you will get diminishing returns," said principal investigator and co-corresponding author Facundo Batista, PhD. "Braking the further development of already effective binders redirects the germinal centers to other targets. Antibodies themselves are thus driving antibody diversity and a broader response."

The findings offer new considerations for vaccine design strategies that aim to generate both potent and broad immune responses.