Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Abstract

Abstract We previously reported that RO+ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD−CD38+ GC B cells, into different fractions based on RB expression. Although each subset contained RB+ cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB+ GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB- and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM+IgD+CD38+CD27−) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD−CD38++CD27+) and memory (IgD−CD38−CD27+) transition. Interestingly, RB+ GC B cells showed increased signs of terminal differentiation toward CD27+ post-GC early plasmablast (increased CD38 and RO) or early memory (decreased CD38 and RO) B cells. We propose that as in T cells, differential RB expression directly correlates with development- and function-based transitions in tonsillar B cells. Application of this RB:RO system should advance our understanding of normal B-cell development and facilitate the isolation of more discrete B-cell populations with potentially different propensities in disease pathogenesis.