TLR7/8 and TLR9 ligands induce phenotypic and transcriptional changes in human transitional B cells

Abstract

Abstract The maturation of human transitional B cells into mature, naïve follicular or marginal zone B cells is a key step in B cell development. Transitional B cells are a prominent B cell population in newborns and very young children who receive many vaccines during early childhood. Pattern recognition receptor (PRR) ligands are attractive candidate vaccine adjuvants due to their targeted mechanisms of action. However, the effects of PRR ligands on transitional B cell fate are not fully understood. We have demonstrated that human cord blood transitional B cells predominantly mature into follicular-like B cells when stimulated in vitro with R848 (TLR7/8 ligand) or CpG (TLR9 ligand) in the presence of IL-4. Additionally, we have profiled the transcriptome of human transitional, follicular and marginal zone-like B cells and identified genes uniquely associated with each B cell subset. Several of the genes identified during our transcriptome analysis were expressed in our in vitro-stimulated transitional B cells. These gene expression changes following PRR ligand stimulation indicate that differing stimuli can skew transitional B cell fate. Our characterization of PRR ligand-induced phenotypic and transcriptional changes associated with mature follicular and marginal zone B cell development may influence the rational approach for vaccine adjuvant development, especially for newborns and very young children.