Role of activin A in negative regulation of normal and tumor B lymphocytes

Activin A, a member of the transforming growth factor β superfamily, has a wide spread expression pattern and pleiotropic functions. In thisoverview we summarize data that points to a role of activin A innegative regulation of B lineage lymphocytes. Experiments performed byus and by other groups revealed the capacity of activin A to causeapoptotic death of tumor myeloma cells, through mechanisms of cellcycle inhibition and antagonism with the survival signal ofinterleukin‐6. In vitro studies on B lymphocyte generation from bonemarrow stem cells and use of human nasal polyps as a model of inflamedtissue further demonstrate an inhibitory role of activin A in B cellspread and accumulation. These data are analyzed with respect to ourmodel of tissue organization that we term the “restrictin model ofcell growth regulation.” This model assumes a morphogen‐like role ofactivin A in the hematopoietic system. Thus, the relative concentrationof biologically functional activin A, in different parts of the tissue, may determine the local B cell content and functional state of thesecells within a specific microenvironment.