Checkpoints in memory B-cell evolution.

We consider four sequential phases in the evolution and consolidation of high affinity B-cell memory as it is regulated in a cognate manner by antigen-specific T-helper (Th) cells. Sequential developmental checkpoints control cell fate in each phase of the pathway in ways that still remain poorly understood. The cellular composition and molecular attributes of each checkpoint are of great interest, but they may vary substantially depending on the nature of the immune stimulus. How this stimulus cascades through the innate and then the adaptive immune responses defines initial effector mechanisms in both Th and B-cell compartments. The germinal center reaction controls memory B-cell development with roles for antigen presentation and cognate Th cell regulation in the establishment of the memory B-cell compartment. Antigen re-challenge rapidly promotes effector responses from the memory compartments of both Th and B cells. Importantly, re-challenge also expands and consolidates immune memory at the serological and cellular levels. We review recent advances in our understanding of memory B-cell evolution with emphasis on the regulatory checkpoints that control lymphocyte fate at each developmental juncture.