Figure 1.
Speculative model for the formation of plasmablast and nonplasmablast committed memory B cells. The figure depicts the primary and secondary B-cell response to a T-cell-dependent protein antigen indicated by the small black squares. Time advances to the right in the diagram. During the primary response, signals from helper T cells and antigen-binding to the B-cell receptor (BCR) drives a naïve B cell to proliferate and produce antibody-secreting plasmablasts and germinal center (GC)-independent memory cells with unmutated and relatively low-affinity BCRs. These memory cells lack CD80, PD-L2, and CD73 and retain the capacity to produce GC cells during secondary responses, at least in the absence of antigen-clearing antibodies. GC cells form a bit later and undergo BCR somatic mutation and compete for antigen and helper T cells, and eventually generate long-lived plasma cells and two kinds of memory B cells, one expressing CD80, PD-L2, and CD73 and one expressing some but not all of these markers. The memory cells expressing CD80, PD-L2, and CD73 likely have the highest affinity BCRs and are committed to rapid production of plasmablasts during secondary responses, whereas the cells expressing some but not all of the markers likely have intermediate affinity BCRs and the potential to rapidly produce plasmablasts and later GC cells. The antigen is then cleared and a year passes, during which the memory B cells and plasma-cell-derived antibodies persist. The antigen then enters the body and much of it is immediately cleared by the existing antibodies. The limited amount of antigen prevents the GC-independent memory cells with low-affinity BCRs from responding at all. The low amount of antigen is sufficient to activate memory cells with increased BCR affinity, and these are likely to be the memory cells that express all or some of the markers. The CD80/PD-L2/CD73+ memory cells then rapidly produce plasmablasts but no GC cells, whereas the memory cells that express some of the markers form GC cells in addition to plasmabasts, eventually leading to the formation of new memory cells with more BCR mutations and higher affinity for the antigen.