Germinal centers: programmed for affinity maturation and antibody diversification

- GCs can support B cells with a range of affinities for the inducing antigen.
- GC selection involves a LZ bottleneck and differential expansion in the DZ.
- Transition between DZ and LZ states is guided by a timed gene expression program.
- Redemption of self-reactive B cells through SHM contributes to antibody diversity.

The seminal discovery by Eisen that antibodies undergo improvements in antigen-binding affinity over the course of an immune response led to a long running search for the underlying mechanism. Germinal centers in lymphoid organs are now recognized to be critically involved in this phenomenon, known as antibody affinity maturation. As well as improving in affinity for specific epitopes, some antibody responses maintain or even increase their breadth of antigen-recognition over time. This has led to another intense line of research aimed at understanding how broadly neutralizing anti-pathogen responses are generated. Recent work indicates that germinal centers also play an important role in the diversification process. We discuss current understanding of how germinal centers are programmed to support both affinity maturation and antibody diversification.