Expression of CD19 and CD20 during human B-cell development. B cells emerge from hematopoietic stem cells (HSC) and acquire maturity in the bone marrow (BM). During this process, CD19 expression starts at the stage of late pro-B cells and precedes that of CD20, starting in immature B cells. CD19 and CD20 expression is maintained during B-cell differentiation and activation in the periphery, while activation and differentiation into memory B cells may fine-tune expression levels. During activation of B cells in lymphoid organs - such as the spleen and tonsil, resulting in their differentiation into plasmablasts and finally plasma cells - CD20 expression is downregulated and subsequently lost. At the same time, CD19 expression is partially downregulated but not extinguished. Being released into circulation, only few plasmablasts express low amounts of CD20, while most have lost CD20 expression but express CD19. After successful immigration into deposits in the BM or the lamina propria (LP), all plasma cells lack CD20, while CD19 expression is maintained by one subset of tissue-resident plasma cells, while another subset acquires a CD19-/CD20- phenotype. Other surface molecules such as CD27, CD38 and CD138 do not qualify as therapeutic targets for global B-cell depletion approaches, as these are not continuously expressed throughout B-cell differentiation and their expression is shared with, for example, T lymphocytes and endothelial cells.