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Department of Molecular Cell Biology, the Weizmann Institute of Science, Rehovot, Israel
Correspondence: Dov Zipori, Ph.D., Department of Molecular Cell Biology, Rehovot 76100, Israel. E-mail: dov.zipori{at}weizmann.ac.il
Activin A, a member of the transforming growth factor ß superfamily, has a wide spread expression pattern and pleiotropic functions. In this overview we summarize data that points to a role of activin A in negative regulation of B lineage lymphocytes. Experiments performed by us and by other groups revealed the capacity of activin A to cause apoptotic death of tumor myeloma cells, through mechanisms of cell cycle inhibition and antagonism with the survival signal of interleukin-6. In vitro studies on B lymphocyte generation from bone marrow stem cells and use of human nasal polyps as a model of inflamed tissue further demonstrate an inhibitory role of activin A in B cell spread and accumulation. These data are analyzed with respect to our model of tissue organization that we term the "restrictin model of cell growth regulation." This model assumes a morphogen-like role of activin A in the hematopoietic system. Thus, the relative concentration of biologically functional activin A, in different parts of the tissue, may determine the local B cell content and functional state of these cells within a specific microenvironment.
Key Words: signal transduction • IL-6 • restrictins • myeloma
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