The early steps of differentiation of human B cells into plasma cells are poorly known. We report a transitional population of CD20 low/− CD38− preplasmablasts along differentiation of human memory B cells into plasma cells in vitro. Preplasmablasts lack documented B cell or plasma cell (CD20, CD38, and CD138) markers, express CD30 and IL-6R, and secrete Igs at a weaker level than do plasmablasts or plasma cells. These preplasmablasts further differentiate into CD20− CD38 high CD138− plasmablasts and then CD20− CD38 high CD138+ plasma cells. Preplasmablasts were fully characterized in terms of whole genome transcriptome profiling and phenotype. Preplasmablasts coexpress B and plasma cell transcription factors, but at a reduced level compared with B cells, plasmablasts, or plasma cells. They express the unspliced form of XBP1 mRNA mainly, whereas plasmablasts and plasma cells express essentially the spliced form. An in vivo counterpart (CD19+ CD20 low/− CD38− IL-6R+ cells) of in vitro-generated preplasmablasts could be detected in human lymph nodes (0.06% of CD19+ cells) and tonsils (0.05% of CD19+ cells). An open access “B to Plasma Cell Atlas,” which makes it possible to interrogate gene expression in the process of B cell to plasma cell differentiation, is provided. Taken together, our findings show the existence of a transitional preplasmablast population using an in vitro model of plasma cell generation and of its in vivo counterpart in various lymphoid tissues.