Splenic Dendritic Cells and Macrophages Drive B Cells to Adopt a Plasmablast Cell Fate

Abstract

Upon encountering cognate antigen, B cells can differentiate into short-lived plasmablasts, early memory B cells or germinal center B cells. The factors that determine this fate decision are unclear. Past studies have addressed the role of B cell receptor affinity in this process, but the interplay with other cellular compartments for fate determination is less well understood. Moreover, B cell fate decisions have primarily been studied using model antigens rather than complex pathogen systems, which potentially ignore multifaceted interactions from other cells subsets during infection. Here we address this question using a Plasmodium infection model, examining the response of B cells specific for the immunodominant circumsporozoite protein (CSP). We show that B cell fate is determined in part by the organ environment in which priming occurs, with the majority of the CSP-specific B cell response being derived from splenic plasmablasts. This plasmablast response could occur independent of T cell help, though gamma-delta T cells were required to help with the early isotype switching from IgM to IgG. Interestingly, selective ablation of CD11c+ dendritic cells and macrophages significantly reduced the splenic plasmablast response in a manner independent of the presence of CD4 T cell help. Conversely, immunization approaches that targeted CSP-antigen to dendritic cells enhanced the magnitude of the plasmablast response. Altogether, these data indicate that the early CSP-specific response is predominately primed within the spleen and the plasmablast fate of CSP-specific B cells is driven by macrophages and CD11c+ dendritic cells. Show more