Antisense macrophage migration inhibitory factor (MIF) prevents anti-IgM mediated growth arrest and apoptosis of a murine B cell line by regulating cell cycle progression.
Macrophage migration inhibitory factor (MIF) is involved in the generation of cell-mediated immune responses. Recently it has been reported that MIF also plays a role in cell proliferation and differentiation. In the present study, using a B-cell line, WEHI-231, and its stable MIF-antisense transfectant, WaM2, as a representative transfectant, we investigated the mechanism underlying regulation of the cell growth by MIF. WaM2 cells produced less MIF than vector control or parental WEHI-231 cells. Reduced and increased proportions were seen in G1 and S-phase cells, respectively, in WaM2 as compared with WEHI-231. Growth arrest and apoptosis after stimulation via surface Ig (sIg) were less prominent in WaM2 cells than those in WEHI-231. However, the addition of recombinant rat MIF did not reverse the inhibition of the growth arrest and apoptosis induced in WaM2 by cross-linking sIg. Almost the same amount of p27kip1 expression was detected in WaM2 cells as those in WEHI-231 and vector control cells. Cross-linking of sIg elevated the p27kip1 level equally in these cells irrespective of the MIF-antisense expression. Taken together, it seems that MIF plays a role in inducing apoptosis in B cells upon IgM cross-linking by regulating the cell cycle via a novel intracellular pathway.
Takahashi
A
A
Section of Pathology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Iwabuchi
K
K
Suzuki
M
M
Ogasawara
K
K
Nishihira
J
J
Onoé
K
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016373:DNA, Antisense; D007075:Immunoglobulin M / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D016373:DNA, Antisense; D007075:Immunoglobulin M; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; D018844:Cyclin-Dependent Kinases