Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation.

In this study, we report that antigen-specific CD19CD27CD21 (CD21) B cells are transiently induced 14 to 28 days after immunization, at the time germinal centers (GCs) peak. Although clonally related to memory B cells and plasmablasts, CD21 cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21 cells express a transcriptional program, suggesting that they are primed for plasma cell differentiation and are refractory to GC differentiation, although they do not spontaneously secrete antibody. In addition, CD21 cells differentially express multiple cell surface markers and have elevated intracellular levels of Blimp-1 and T-bet protein compared with memory B cells. Together, these data support a model in which CD21 cells are recent GC graduates that represent a distinct population from CD27 classical memory cells, are refractory to GC reentry, and are predisposed to differentiate into long-lived plasma cells.