A study tracking thousands of B cells across more than 100 germinal centers (GCs) in mice has revealed how the system consistently produces highly effective antibodies. The findings overturn longstanding ideas about how germinal centers function, revealing that they are far more selective than once thought, and challenge the idea that antibody improvement is driven mainly by rare growth “bursts” among the most successful B cells. The discovery could have implications for immune cell evolution, and ultimately guide the design of vaccines against rapidly mutating pathogens like influenza. It could also lead to new ways of studying evolution itself. “The traditional, mechanistic view of germinal centers is to think of them as selection machines sorting out the best antibodies,” said research lead Gabriel D. Victora, PhD, head of the Laboratory of Lymphocyte Dynamics at The Rockefeller University. “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.” Victora and colleagues reported on their findings in Cell, in a paper titled “Replaying germinal center evolution on a quantified affinity landscape.” Inside germinal centers, B cells rapidly mutate and compete to produce antibodies that bind successively better to pathogens. “Darwinian evolution of immunoglobulin genes within germinal centers (GCs) underlies the progressive increase in antibody affinity following antigen exposure,” the authors wrote. That puts…
