Induction of ornithine decarboxylase activity in mouse B lymphocytes.

Induction of ornithine decarboxylase activity in mouse B lymphocytes.
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诱导小鼠 B 淋巴细胞中鸟氨酸脱羧酶活性。

DOI:
10.1093/intimm/6.11.1777
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发表时间:
1994
影响因子:
4.4
通讯作者:
Ashman,R
Ashman,R
中科院分区:
医学3区
文献类型:
--
作者:
Molitor,J;Pace,W;Stunz,L;Vigna,J;Louie,S;Ashman,R

文献摘要

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We have examined the role in B cell activation of ornithine decarboxylase (ODC), the labile ratelimiting enzyme in the synthesis of polyamlnes thought to be required for S phase entry in all cells. When small resting mouse splenic B cells were stimulated with the mitogenic agents phorbol myristate acetate (PMA) plus lonomycin (lo), LPS or the B cell specific agent F(ab′)2anti-lg, ODC activity was greatly increased. ODC activity in small dense B cells remained near baseline levels for the first 6 h after treatment with LPS, but then increased ∽150-fold In the next 18 h. When purified B cells were not separated by cell density, ODC activity was 30-fold greater at baseline and rose earlier after LPS stimulation, reaching a level about three times that of LPS-stimulated small, dense B cells at 24 h, implying that large (preactivated) B cells have much greater ODC responses than small, dense B cells. ODC activity, like S phase entry, could also be induced in small, dense B cells by PMA and lo but failed to respond to either agent alone. ODC levels rose transiently by ∽40-fold between 2 and 6 h following stimulation of small B cells with F(ab′)2anti-ig, then declined to baseline. Whole anti-ig did not stimulate ODC activity and also blocked the F(ab′)2anti-ig mediated increase in ODC activity, just as it produced the expected inhibition of thymidrne incorporation and cellular progression into S phase. Although IL-4 provided the expected restoration of thymldlne incorporation and S phase progression in response to whole anti-ig, it failed to restore the ODC response, providing a striking example of cell cycle entry without increased ODC activity. ODC mRNA levels were not affected in proportion to ODC activity. Except for the 2-fold increase in ODC mRNA seen with PMA and to, changes in steady-state ODC mRNA levels were remarkably absent inhibition of ODC by difluoromethylornithlne had little effect on steady-state mRNA levels for transferrin receptor, IL-2 receptor α, class II MHC (la), CD23 or ODC itself, with or without PMA and lo. Thus, in the B cell, a large ODC activity increase was a common but not invariable harbinger of cell cycle entry, changes in steady-state ODC mRNA levels were small or absent, QDC induction showed PMA-lo. synergy and ODC did not appear to regulate the mRNA levels of other activation markers.