Shibuya T, Niho Y, Mak T W
J Exp Med. 1982 Aug 1;156(2):398-414. doi: 10.1084/jem.156.2.398.
This report confirms that the Fv-5 locus controls the types of erythropoiesis induced by Friend erythroleukemia virus (FLV) (21) and extends the study to investigate the mode of action of this locus. With the use of FLV obtained by a variety of procedures, we showed that the polycythemia spleen focus-forming component (SFFVp) was responsible for the contrasting changes of hematocrits observed in FV-Pp (polycythemia strain)-infected DBA/2 (Fv-5pp) or CBA (Fv-5aa) mice. These changes in hematocrits were found to be a direct result of the rise in circulating reticulocytes and erythrocytes in DBA/2 mice and a corresponding drop of these erythroid cells in CBA mice 2 wk after infection. Examination of the FV-P-induced cellular changes indicated that dramatic increase in erythropoietin (epo)-independent erythroid precursor (CFU-E*) cells was detected in the spleens and marrow of both strains of mice. The epo responsiveness of the CFU-E in the uninfected and FV-P-infected CBA and DBA/2 mice was also very similar. Similar to FLV-infected DBA/2 mice, the FV-P-infected CBA mice also developed tumorogenic cells (CFU-FV) relatively early after infection (4-6 wk). Study of the physiological and pathological changes in the marrows and spleens of these infected mice indicated that significant differences were found in the spleens of the two strains of mice. The percent of reticulocytes in the spleen cells of CBA mice remained between 10 and 20%, and level of the DBA/2 mice increased to approximately 50%. This higher rate of erythropoiesis was also reflected in the significantly higher rate of uptake of 59Fe in the spleens of the DBA/2 mice. These results suggest that the Fv-5 locus might control the hematocrit levels of these mice by regulating the rates of erythropoiesis in the spleen levels of these mice, probably by affecting the rate of proliferation of an erythroid cell or cells. The erythroid cell(s) affected is likely to be more mature than the erythroid progenitor, CFU-E, as the levels of CFU-E in these two strains of mice were similar. The hypothesis that Fv-5 may control the rates of proliferation of a late erythroid (cell(s) is also supported by the significantly higher spleen weights found in the infected DBA/2 (approximately 2.5 g/spleen) mice than in the CBA (approximately 1 g/spleen) strain.
本报告证实Fv - 5基因座控制着由弗瑞德氏白血病病毒（FLV）诱导的红细胞生成类型（21），并将研究扩展至探究该基因座的作用模式。通过使用多种方法获得的FLV，我们发现多血症脾集落形成成分（SFFVp）是导致FV - Pp（多血症株）感染的DBA/2（Fv - 5pp）或CBA（Fv - 5aa）小鼠中观察到的血细胞比容对比变化的原因。这些血细胞比容的变化被发现是感染后2周时DBA/2小鼠循环网织红细胞和红细胞增加以及CBA小鼠中这些红系细胞相应减少的直接结果。对FV - P诱导的细胞变化的检查表明，在两种品系小鼠的脾脏和骨髓中均检测到促红细胞生成素（epo）非依赖性红系前体细胞（CFU - E*）显著增加。未感染和FV - P感染的CBA和DBA/2小鼠中CFU - E对epo的反应性也非常相似。与FLV感染的DBA/2小鼠类似，FV - P感染的CBA小鼠在感染后相对较早（4 - 6周）也产生了致瘤细胞（CFU - FV）。对这些感染小鼠的骨髓和脾脏的生理和病理变化的研究表明，在两种品系小鼠的脾脏中发现了显著差异。CBA小鼠脾细胞中网织红细胞百分比保持在10%至20%之间，而DBA/2小鼠的水平增加到约50%。这种较高的红细胞生成率也反映在DBA/2小鼠脾脏中59Fe摄取率显著更高。这些结果表明，Fv - 5基因座可能通过调节这些小鼠脾脏中的红细胞生成率来控制这些小鼠的血细胞比容水平，可能是通过影响一个或多个红系细胞的增殖率。受影响的红系细胞可能比红系祖细胞CFU - E更成熟，因为这两种品系小鼠中CFU - E的水平相似。Fv - 5可能控制晚期红系细胞（一个或多个）增殖率的假设也得到了感染的DBA/2（约2.5克/脾脏）小鼠比CBA（约1克/脾脏）品系脾脏重量显著更高的支持。
