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The Mesenchymal Stroma Negatively Regulates B Cell Lymphopoiesis through the Expression of Activin A
Author(s) -
SHOHAM TSIPI,
PARAMESWARAN RESHMI,
SHAVTAL YARON,
BARDASAAD MIRA,
ZIPORI DOV
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb03253.x
Subject(s) - lymphopoiesis , haematopoiesis , mesenchymal stem cell , biology , b cell , spleen , bone marrow , activin type 2 receptors , acvr2b , microbiology and biotechnology , in vivo , endocrinology , medicine , tgf beta signaling pathway , immunology , stem cell , antibody , transforming growth factor
A bstract : The negative control of B cell generation is only partially resolved. We assessed the role of activin A in regulation of B lymphopoiesis in view of its specific inhibitory effects on tumor B lineage cells. Activin A is constitutively expressed in mouse hemopoietic organs and in cultured mesenchymal cell lines. We observed an inverse relationship between activin A titer and B lineage cell production. In the spleen, the red pulp exhibited a relatively higher abundance of the protein as compared with the lymphoid follicles, wherein B cell accumulation occurs. Furthermore, a specific shut off in activin A expression was observed in bone marrow and spleen following in vivo induction of B lymphocyte polyclonal activation. We further substantiated these in vivo observations by in vitro studies of primary bone marrow cultures, in which the expression of functional activin A was found to be diminished prior to the onset of B lymphopoiesis. The reduction in functional activin A is shown to concomitantly occur with spontaneous induction of the expression of activin A specific inhibitors. We therefore propose that the mesenchymal organ stroma expresses activin A that negatively controls B cell lymphopoiesis.