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

Abstract

In this study, we report that antigen-specific CD19+CD27+CD21lo (CD21lo) B cells are transiently induced 14-28 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 they are primed for plasma cell differentiation and are refractory to GC differentiation, although they do not spontaneously secrete antibody. Additionally, CD21lo cells differentially express multiple cell surface markers and have elevated intracellular levels of Blimp-1 and T-bet protein compared to 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.

T‐bet+ memory B cells: Generation, function, and fate

“…76 Loss of HA-specific IgG2 a via T-bet + B cell depletion abolishes serum antibody HA stalk reactivity, suggesting T-bet − B cells are unable to compensate by producing stalk-reactive antibody. 37,39,40,49,54 Parabiosis experiments with an infected mouse and uninfected congenic partner further suggest splenic HA-specific T-bet + B cells are largely resident; while it is unclear if some T-bet + B cells or their descendants leave this tissue, the absence of donor T-bet + B cells in the spleen of conjoined mice indicates this subset does not re-enter the spleen from blood. [82][83][84] It has recently emerged that T-bet + and T-bet − memory B cells differ in their trafficking and localization abilities.…”

“…[6][7][8][9][10] Analogous broad categories also exist among antigen-experienced cells of the B lineage-memory B cells (Bmem) and antibodysecreting plasma cells (PC)-and reports of subdivisions within these groups have emerged in the last several years. 26,[35][36][37][38][39][40][41] In this article, we first review the discovery and general characteristics of T-bet + memory B Summary B cells expressing the transcription factor T-bet have emerged as participants in a number of protective and pathogenic immune responses. [17][18][19][20] Within this context, a B cell subset expressing the transcription factor T-bet has been the focus of increasing interest in the last several years, reflected by numerous commentaries and dedicated overview volumes.…”

Early B cell changes predict autoimmunity following combination immune checkpoint blockade

“…CD21 lo B cells were recently described as new germinal center emigrants primed for plasma cell differentiation (15) and showed an overlap with tissue-homing, innate-like B cells (16). These properties position CD21 lo B cells as being capable of rapid activation following checkpoint blockade and causing tissue injury.…”

Germinal center responses to complex antigens

“…These conditions are not trivial, as the first refutes the notion of “open” GCs (50), and the second is incompatible with a role for circulating Ab in driving affinity maturation (51). Indeed, B cells that exit GCs become refractory to GC re-entry for weeks (52). Our preferred explanation is that the driving forces of affinity maturation are sufficiently permissive to support individual GCs populated with clones having substantially different (10- to 100-fold) BCR affinities for antigen, even late in the immune response.…”