B Cell Selection in Antibody Production: Affinity Rules, but Diversity Matters

Affinity for antigen is a fundamental parameter of humoral immunity. It determines the B cell clones that participate in the response, it is a readout of clonal selection as the response progresses, and the magnitude of its improvement in T cell-dependent responses is a major criterion of success. But another important attribute of immunity at initiation, propagation, and cessation is the diversity of antigen binding by B cells and antibodies. As such, the diversity of antigen receptors is important at the outset of the response in providing a broad population from which B cell fates can be selected. Equally, within the germinal center, specific mechanisms operate to diversify the B cell population for affinity-based selection, which itself promotes clonal restriction to achieve its goals. However, the importance of sustaining diversity of antigen recognition at all stages of the response, not only in the composition of the B cell memory compartments, is often lost by the focus on affinity as the key measure of immunity. In this article, we consider recent developments in understanding B cell selection into, persistence within, and exit from T cell-dependent immune responses and how these processes are calibrated to ensure diversity of antigen recognition persists into memory in spite of the clonal narrowing that is the usual outcome of affinity-driven selection.