How germinal centers make stronger antibodies ^{CEFR B2}

To study antibody evolution precisely, Gabriel D. Victora’s group engineered mice so that all competing B cells began with the same unmutated antibody sequence and then induced germinal center formation by immunization. The team combined multiphoton microscopy, laser-based photoactivation and extensive DNA sequencing to follow thousands of individual B cells across 119 germinal centers and to build detailed lineage trees.

They created a mutational dictionary using Deep Mutational Scanning (DMS). DMS links almost every possible amino-acid change to antibody performance, which let the researchers infer a cell’s binding strength and structural stability from its DNA sequence. “DMS was the big technical advance here,” said first author Ashni Vora.

Within a single germinal center the pattern of evolution often looked nearly random: some clones expanded, others disappeared, and promising mutations sometimes failed to win. Some centers experienced clonal bursts while others maintained many competing lineages, and success often correlated poorly with affinity.

However, repeated noisy rounds of selection across many germinal centers produced a clear, predictable gain in antibody quality. The system shows a small bias toward beneficial mutations and also tends to favor changes that the cellular machinery can make more easily, rather than always choosing the theoretically strongest mutations. These findings overturn assumptions about germinal-center function, may help guide vaccines against fast-mutating pathogens such as influenza and HIV, and suggest the immune response could serve as a model for studying evolution. Source: Rockefeller University.