Functionally Distinct Subpopulations of CpG-Activated Memory B Cells

Abstract

During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27(lo) subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27(hi) plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27(lo) and proliferating CD27(hi) subpopulations. Our data supported an alternative hypothesis, that CD27(lo) cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27(lo) and CD27(hi) Bc differentiation.