Selection in the germinal center

Germinal centers (GCs) are well known for their important role in shaping the secondary B cell repertoire to generate antibodies capable of binding with high-affinity and specificity to foreign antigens. Somatic hypermutation of the Ig variable region genes in GC B cells represents a highly efficient mechanism for generating new antibody variants with increased antigen affinity. To be effective, however, this process needs to be intimately linked with equally efficient processes that positively select high-affinity clones for perpetuation in the GC and, ultimately, for differentiation into plasma cell and memory B cell effector populations. Just as important is the need for mechanisms of negative selection that remove GC B cell clones with unwanted specificities, particularly those that have gained reactivity with self-components. Here, we discuss recent advances in our understanding of the various selective processes that occur within the GC and identify the major questions in this field that remain to be answered.