Characterization of activated B cells, a novel antigen-specific B cell population that emerges in blood after infection and vaccination in humans (VAC11P.1062)

Abstract

Abstract Plasma cells (PCs) and memory B cells (MBCs) provide a remarkably stable humoral immune memory. In humans, antigen-specific antibody secreting cells (ASCs) and MBCs are detected in peripheral blood shortly after infection and vaccination. While ASCs can be distinguished by surface staining, the phenotype of recently generated MBCs is unknown. Here, we defined the phenotype of the latter cells, and termed them activated B cells (ABCs). We confirmed the specificity of ABCs after influenza vaccination and infection by ELISPOT (after in vitro differentiation) and by HA-specific staining. Similarly to ASCs, ABCs actively proliferate, up-regulate CD27 and down-regulate CD21. In contrast to ASCs, ABCs do not spontaneously secrete antibodies and up-regulate CD20 expression. ABCs represent a distinct lineage from ASCs as they maintained Pax5 expression and showed only a slight increase in IRF4 expression compared to naive B cells. Using this characterization, we were able to clearly distinguish ABCs and ASCs in peripheral blood of two Ebola virus-infected patients who were being cared for at Emory University Hospital. Defining ABCs is critical for addressing basic questions regarding the fundamental differences between the memory and plasma cell compartments in humans and because ABCs could be used for procuring therapeutic monoclonal Abs that may be different in terms of their protective potential from those derived from ASCs.