Research ArticlePLASMA CELLS

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

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Science Immunology  27 Jan 2017:
Vol. 2, Issue 7, eaai8153
DOI: 10.1126/sciimmunol.aai8153

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Plasma cell precursors

Memory B cells are critical players in the rapid secondary immune response to pathogens; however, little is known about B cell subsets that are phenotypically different from classical memory populations. Now, Lau et al. report that CD21lo B cells in healthy humans are predisposed to differentiate into long-lived plasma cells. CD21lo B cells were induced during the peak of germinal center (GC) activity after influenza vaccination but formed distinct clades from memory B cells and plasmablasts. These cells were primed for plasma cell differentiation but resistant to further GC differentiation. These data suggest that CD21lo cells are a distinct population of memory B cells that may contribute to plasma cell formation.

Abstract

In this study, we report that antigen-specific CD19+CD27+CD21lo (CD21lo) 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, CD21lo cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21lo 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, CD21lo 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 CD21lo 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.

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