Rockefeller University researchers published a study in the journal Cell in 2026 concluding that germinal center selection relies on repeated statistical bias. The research found that this process occurs instead of isolated rapid expansion events. The study tracked thousands of B cells across 119 germinal centers in mice.
The research team engineered mice so that competing B cells began with an identical unmutated antibody sequence. Germinal center formation in these mice was initiated through immunization. Scientists utilized multiphoton microscopy and laser-based photoactivation to track B cell development. Researchers also sequenced thousands of individual B cells across the germinal centers studied and constructed a lineage family tree to map B cell development.
The study found that individual B cell expansion within a single germinal center demonstrated a low correlation between antibody binding strength and evolutionary success. The immune system preferentially generates mutations that are biochemically easier to produce. These are not necessarily the mutations that would maximize antibody binding strength. Germinal centers rapidly remove B cells with lower binding affinity.
Gabriel D. Victora, head of the Laboratory of Lymphocyte Dynamics at Rockefeller University, commented on the findings. Victora said, "The traditional, mechanistic view of germinal centers is to think of them as selection machines sorting out the best antibodies. But when you look very, very closely, you see a process that's almost essentially random-a little bit better than a coin toss-which repeats many times until the immune system arrives at the right answer consistently. That's much more akin to how evolution operates than the way a machine does."
The study also utilized Deep Mutational Scanning (DMS) to associate specific amino-acid changes with antibody performance metrics. Ashni Vora, the study's first author and a graduate fellow in the laboratory, said, "DMS was the big technical advance here. With it we could determine the affinities of thousands of cells just by looking at their sequence, without having to produce an antibody." The research suggests the germinal center model could be applied to study evolutionary biology.
No independent assessment was available for this report.