Fülöp G, Lee M Y, Rosse C
J Immunol. 1985 Dec;135(6):4266-72.
Mice bearing a transplantable CE mammary carcinoma have been shown to have greatly augmented rates of neutrophil production coupled with a marked diminution of bone marrow lymphocytes. The objective of the present study was to test whether the loss of lymphocytes, and especially of B cells, from the bone marrow and spleen of tumor-bearing animals was due to a reduced rate of cell production and if so, at what level this response was regulated. A modified 3H-TdR pulse and chase analysis was used to assess the rates of production of small lymphocytes and B cells (stained for c mu and s mu) at weekly intervals after CE tumor transplantation. 3H-TdR was infused continuously for 24 hr, and radioautographs were prepared of bone marrow and spleen cells 0, 24, and 48 hr after termination of the infusion. Pre-B cells (c mu+s mu-) essentially disappeared from the femoral bone marrow by the end of 1 wk of tumor growth, followed by a great reduction in the number of c mu+s mu+ cells in the marrow and s mu + cells in the spleen. Although pre-B cells appeared in the peripheral marrow (caudal vertebrae, metatarsal bones) and spleen of tumor-bearing mice, these cells could not compensate for the continued decrease in the numbers of more mature B cells. In normal mice, during the 48-hr chase period, newly formed, 3H-TdR-labeled, small lymphocytes and s mu+ cells continued to emerge from the prelabeled precursor compartment at a steady rate, but after 1 wk of tumor growth, the number of small lymphocytes and s mu+ cells emerging from the precursor compartment fell steadily during the 48-hr chase period. During the second and third weeks of tumor growth, a steady state appears to have been reached in B cell production, which was at a level approximately 10 times below that of normal. Because pre-B cells are normally maintained by a less mature precursor population (2), the initial disappearance of c mu+s mu- cells suggests that the CE mammary carcinoma exerts its modulatory influence on primary B cell production by inhibiting or eliminating the cells that eventually feed into the pre-B compartment. The nature of the regulatory factors apparently secreted by the tumor and the more precise identity of the target cells are under investigation.
携带可移植CE乳腺癌的小鼠已被证明中性粒细胞生成率大幅提高，同时骨髓淋巴细胞显著减少。本研究的目的是测试荷瘤动物骨髓和脾脏中淋巴细胞尤其是B细胞的减少是否是由于细胞生成率降低，如果是，这种反应在何种水平受到调节。采用改良的3H-TdR脉冲追踪分析，在CE肿瘤移植后每周评估小淋巴细胞和B细胞（用c mu和s mu染色）的生成率。连续24小时注入3H-TdR，并在注入结束后0、24和48小时制备骨髓和脾细胞的放射自显影片。肿瘤生长1周结束时，前B细胞（c mu+s mu-）基本从股骨骨髓中消失，随后骨髓中c mu+s mu+细胞和脾脏中s mu +细胞数量大幅减少。虽然前B细胞出现在荷瘤小鼠的外周骨髓（尾椎、跖骨）和脾脏中，但这些细胞无法弥补更成熟B细胞数量的持续减少。在正常小鼠中，在48小时的追踪期内，新形成的、3H-TdR标记的小淋巴细胞和s mu+细胞以前体标记区室稳定的速率持续出现，但肿瘤生长1周后，在前体标记区室出现的小淋巴细胞和s mu+细胞数量在48小时的追踪期内稳步下降。在肿瘤生长的第二和第三周，B细胞生成似乎达到了稳定状态，其水平比正常水平低约10倍。由于前B细胞通常由不太成熟的前体细胞群体维持，c mu+s mu-细胞的最初消失表明CE乳腺癌通过抑制或消除最终进入前B区室的细胞，对原发性B细胞生成施加调节影响。肿瘤明显分泌的调节因子的性质以及靶细胞更精确的身份正在研究中。
