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

In this study, we report that antigen-specific CD19⁺CD27⁺CD21^lo (CD21^lo) 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^lo cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21^lo 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^lo 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^lo 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.