GROWTH CONTROL OF ACTIVATED, SYNCHRONIZED MURINE B CELLS BY THE C3D FRAGMENT OF HUMAN COMPLEMENT
GROWTH CONTROL OF ACTIVATED, SYNCHRONIZED MURINE B CELLS BY THE C3D FRAGMENT OF HUMAN COMPLEMENT
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DOI：
10.1038/317264a0
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发表时间：
1985-01-01
期刊：
影响因子：
64.8
通讯作者：
DIERICH, MP
中科院分区：
文献类型：
--
作者：
MELCHERS, F;ERDEI, A;DIERICH, MP
三个限制点控制活化的B淋巴细胞的细胞周期1。第一种直接发生在有丝分裂后，由表面结合免疫球蛋白的占据控制。第二个是在周期的G1期有丝分裂后14 h观察到的，即在DNA复制之前，并且由巨噬细胞2产生的生长因子控制，我们先前将其归类为α型因子3，4。第三个限制点发生在G2期，有丝分裂前2-4小时，并由辅助性T淋巴细胞可能产生的β-型生长因子控制5。补体的第三种成分C3长期以来一直与B细胞反应的控制有关6 -12。C3由单核细胞和巨噬细胞分泌13，14。我们最近发现，交联的，但不可溶的，人C3刺激激活，但不休息，鼠B细胞胸苷摄取15。在这里，我们调查的作用C3 B和C3 d的活化，同步小鼠B细胞的细胞周期的进展。我们发现，交联C3 d取代了这些细胞的细胞周期内的α-因子的作用，并允许进入S期。相反，可溶性C3 d抑制α因子的作用。这意味着C3 d特异性受体，可能是人补体受体CR 2的鼠类似物（参考文献16、17），是活化B细胞上的生长因子受体，当其交联时，将给予细胞生长阳性信号，而可溶性形式的C3 d占据将导致α因子或交联C3 B或C3 d的作用抑制。鼠C3 d的cDNA序列与鼠生长因子的cDNA序列之间的一段弱同源性表明胰岛素样生长因子可能是控制活化的B细胞的细胞周期的C3 d的活性成分。
Three restriction points control the cell cycle of activated B lymphocytes1. The first occurs directly after mitosis and is controlled by the occupancy of surface-bound immunoglobulin. The second is observed ∼4 h after mitosis in the G1phase of the cycle, that is, before DNA replication, and is controlled by growth factors that are produced by macrophages2which we have previously classified asα-type factors3,4. The third restriction point occurs in the G2phase, 2–4 h before mitosis, and is controlled byβ-type growth factors probably produced by helper T lymphocytes5. The third component of complement, C3, has long been implicated in the control of B-cell responses6–12. C3 is secreted by monocytes and macrophages13,14. We have found recently that crosslinked, but not soluble, human C3 stimulates activated, but not resting, murine B cells to thymidine uptake15. Here we investigate the role of C3b and C3d in the progression of the cell cycle of activated, synchronized murine B cells. We find that crosslinked C3d replaces the action ofα-factors within the cell cycle of these cells and allows entry into S phase. In contrast, soluble C3d inhibits the action ofα-factors. This implies that a C3d-specific receptor, probably the murine analogue to the human complement receptor CR2 (refs 16, 17), is a growth factor receptor on activated B cells that will give the cell a growth-positive signal when it is crosslinked, while occupancy by the soluble form of C3d will result in inhibition of the action ofα-factors or of crosslinked C3b or C3d. A stretch of weak homology between the cDNA sequence of murine C3d and those of murine growth factors indicates that an insulin-like growth factor could be the active principle of C3d that controls the cell cycle of activated B cells.