In vitro growth inhibition of murine leukemia cells by antibody specific for the major envelope glycoprotein (gp71) of friend leukemia virus

Eugene V. Genovesi; Jeffrey J. Collins

摘要

AbstractAn in vitro complement (C′)‐independent growth cytostasis model is described in which the replication of Friend leukemia virus (FLV)‐induced erythroleukemia cells (of the FLC‐745 cell line) is inhibited by goat serum directed against the major FLV envelope glycoprotein,gp71. The cytostatic effect is reversible, with the degree of this reversibility dependent on both the concentration and duration of exposure to immune serum. The inhibitory factor in heat‐activated goat anti‐FLVgp71 (δGαFLVgp71) serum has been identified as virus‐specific IgG antibody, and F(ab')2fragments of this antibody are highly effective in suppressing FLC‐745 cell growth. Studies with various murine leukemia and lymphoma cell lines, as well as with a panel of antisera directed against various murine oncornaviruses or viral proteins, have demonstrated that antibodies reactive with the group or type determinants of FLVgp71 are capable of mediating cytostasis. Under conditions of antibody‐mediated growth inhibition of FLC‐745 cells, specific modulation ofgp71 expression is followed by nonspecific modulation of H‐2dantigen expression. In addition, considerable cell death occurs in cytostatic cultures which is accompanied by continued division (as measured by DNA synthesis) of a portion of the cell population. Cytofluorimetric analysis of nuclei from growth‐inhibited FLC‐745 cells demonstrates a diminution in the frequency of cells in the G2/M phase of the cell cycle. It is suggested that antibody‐mediate FLC‐745 cell growth inhibition operates via a blockade of the cell cycle which prevents most cells in the population from traversing G2/M. While these blocked cells appear to be subject to slow cytolysis by a C′‐independent mechanism, a portion of the cells escape this blockade and continue to replicate, thus offsetting the death of the former cells to yield a relatively constant density of viable cells for at least 72–96 h of growth inhibition. The possible relevance of this in vitro phenomenon to in vivo passive therapy against FLV‐induced disease with GαFLVgp71 an

In vitro growth inhibition of murine leukemia cells by antibody specific for the major envelope glycoprotein (gp71) of friend leukemia virus

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