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Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) are mitogens for bipotential oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells. We investigated the mitogenic effect of these growth factors on quiescent mature oligodendrocytes (OL) expressing myelin basic protein (MBP) in OL cultures that were treated for 3 days with cytosine arabinoside (ARA-C) in order to kill O-2A precursors which divide in chemically defined medium. After treatment with ARA-C proliferation decreased and O-2A precursors identified with A2B5 monoclonal antibody were nearly undetectable. After exposure of mature OL to bFGF, cell proliferation increased markedly within 24 hr. PDGF had a much weaker effect. Cultures treated with ARA-C for 3 days and then with bFGF for the next 24 hr and incubated with BrdU for the last 2 hr before the end of the experiment were immunolabeled with anti-MBP or A2B5 and anti-bromodeoxyuridine (BrdU) antibodies. Eighty-seven percent of the cells were MBP+, 10% were both MBP+ and BrdU+, and none was A2B5+ BrdU+, showing that at least a part of the population of mature MBP+ OL retains the ability to reenter the cell cycle in vitro. Since mature OL did not proliferate in response to bFGF in the cultures not treated with ARA-C, i.e., in the presence of O-2A progenitors, we assumed that these precursors were responsible for the lack of mitogenic effect of bFGF on MBP+ OL in such conditions. Conditioned medium from O-2A precursors almost halved the bFGF-induced OL proliferation after treatment with ARA-C, suggesting that O-2A progenitors control the proliferation of a subpopulation of mature OL (possibly young mature OL) via the secretion of active molecule(s).

Both acidic and basic fibroblast growth factor (FGF), although devoid alone of growth-promoting ability on resting or activated human lymphoid B cells, were found to markedly increase the proliferative response of anti-mu-chain or SAC preactivated B cell blasts to the low molecular weight B cell growth factor (LMW-BCGF) and to enhance the costimulatory response of resting B cells to anti-mu-chain and LMW-BCGF. This potentiating effect was also observed for a LMW-BCGF-dependent B cell tumor derived from a lymphocytic nodular lymphoma. Other growth factors acting on fibroblasts, such as epidermal growth factor, alpha-thrombin, platelet-derived growth factor, and insulin-like growth factor-I did not display such enhancing effect on LMW-BCGF-driven proliferation. Activated, but not resting B cells were found to bear receptor sites for FGFs and from kinetics experiments, it is suggested that LMW-BCGF induces competence expression for FGFs in those cells. Moreover, the LMW-BCGF-elicited generation of inositoltrisphosphate resulting from polyphosphoinositides hydrolysis was increased in the presence of FGF.