The mesenchymal stroma negatively regulates B cell lymphopoiesis through the expression of activin A.
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.
Shoham
Tsipi
T
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Parameswaran
Reshmi
R
Shav-Tal
Yaron
Y
Barda-Saad
Mira
M
Zipori
Dov
D
D028341:Activins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D038041:Lymphopoiesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits