Fig. 3
Summary of relationships and potential connections of BCR affinity, selected signals, and fate choices for B cells. As reviewed in the main text, the likelihood that a naive B cell, after its activation, flows into the memory pool, stably participates in a germinal center reaction, or undergoes extrafollicular differentiation directly to a plasma cell fate is influenced by BCR affinity (or avidity) for the antigen (indicated by the triangle and indicator arrow below it). GC B cells also contribute to the overall memory pool, generally after some degree of affinity maturation (not captured in this cartoon). Aspects of the relationship to signaling via ERK and mTORC1 activity are not fully established or settled, e.g., that high mTORC1 activity fosters increased PC differentiation among GC B cells. As discussed in the text, however, ERKhi and mTORC1hi cells appear to be favored for progression toward the PC fate, but whether BCR engagement by higher- versus lower-affinity ligands (antigens) causes heightened ERK or mTORC1 activity is not clear. For the memory pool, which will tend toward a more somatically mutated and selected BCR repertoire, memory cell activation will favor PC differentiation among BACH2lo MBCs, but some activated memory cells do enter a new GC reaction, which in turn can yield new MBCs and ASCs
