(A) B cell development and activation. B cells originate and complete initial phases of differentiation and maturation in the bone marrow. Immature B cells exit the bone marrow and move to the circulation as TR B cells, then complete maturation in the spleen. If activated by antigen and T cell help, these mature preimmune B cells will proliferate and form germinal centers, culminating in the generation of memory and plasma cells that make high-affinity, isotype-switched antibodies. (B) B cell developmental stages and BLyS receptor expression. BLyS dependence ensues at the TR developmental stages, at which BR3 and TACI are first expressed. These receptors remain expressed among all preimmune populations. After antigen-driven activation, BLyS receptor expression shifts to predominantly TACI and/or BCMA expression among memory and long-lived plasma cells (the latter of which permanently reside in bone marrow).