Plasma cells provide humoral immunity. They have traditionally been viewed mainly as short-lived end-stage products of B-cell differentiation that deserve little interest. This view is changing, however, because we now know that plasma cells can survive for long periods in the appropriate survival niches and that they are an independent cellular component of immunological memory. Studies of the biology of plasma cells reveal a mechanism of intriguing simplicity and elegance that focuses memory provided by plasma cells on recently encountered pathogens while minimizing the 'fading' of memory for pathogens encountered in the distant past. This mechanism is based on competition for survival niches between newly generated plasmablasts and older plasma cells.

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Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38. CD38 low IgG-secreting cells were present exclusively in the tonsils. A major fraction of these cells appeared to be early plasma cell precursors, as upon activation of B cells in vitro, IgG secretion preceded up-regulation of CD38, and on tonsillar sections, IgG-containing, CD38 low cells with a plasmacytoid phenotype were found in follicles, where plasma cell differentiation starts. A unitary phenotype of migratory peripheral blood IgG-secreting cells suggests that all bone marrow plasma cell populations share a common precursor cell. These data are compatible with a multistep model for plasma cell differentiation and imply that a common CD38 low IgG-secreting precursor gives rise to a diverse plasma cell compartment.