Normal B cell precursors responsive to recombinant murine IL-7 and inhibition of IL-7 activity by transforming growth factor-beta.
The ability of stromal cells in bone marrow to support B lymphopoiesis may be partially mediated by secretion of biologically active factors. The first cytokine with lymphopoietic activity to be molecularly cloned from stromal cells, IL-7, was originally identified by its growth-promoting activity on long term cultured lymphocytes. We now report that murine rIL-7 is a potent proliferative stimulus for B cell progenitors isolated from fresh bone marrow. Proliferation was initially most obvious among large precursor cells which bear the B lineage associated Ag, Ly5/220 and BP1. A majority of these also contained cytoplasmic Ig mu H chains. Extended culture with IL-7 resulted in a predominance of immature c mu- lymphocytes. No effect by IL-7 was observed on the proliferation of mature lymphocytes. It also did not induce maturation in a number of early B lineage cell lines, or promote the formation of LPS-responsive, clonable B cells from precursors. When incorporated into semisolid agar medium, IL-7 specifically and rapidly induced the formation of pre-B cell colonies in a linear fashion with respect to numbers of cells cultured from either purified B cell progenitor preparations or unfractionated bone marrow. In both liquid and agar culture conditions, the IL-7 proliferative activity was inhibitable by two related forms of transforming growth factor (TGF) beta, TGF-beta 1 and TGF-beta 2. Taken together, these results indicate that IL-7 is a stimulus for replication of normal B lineage cells at an early stage of differentiation, and its activity can be modulated by other cytokines. IL-7 also provides a means of studying the progeny of a single B cell progenitor, and of enumerating clonable pre-B cells in the absence of colony formation by other cell types in bone marrow.
Lee
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G
Oklahoma Medical Research Foundation, Oklahoma City 73104.
Namen
A E
AE
Gillis
S
S
Ellingsworth
L R
LR
Kincade
P W
PW
D000362:Agar; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D003470:Culture Media; D006131:Growth Inhibitors / Q000494:pharmacology*; D015851:Interleukin-7; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000276:immunology*; D015291:Transforming Growth Factors / Q000494:pharmacology*
D003470:Culture Media; D006131:Growth Inhibitors; D015851:Interleukin-7; D007378:Interleukins; D011994:Recombinant Proteins; D015291:Transforming Growth Factors; D000362:Agar