Koropatnick J, Pearson J, Harris J F
Ontario Cancer Treatment and Research Foundation, London Regional Cancer Centre, Canada.
Mol Biol Med. 1988 Apr;5(2):69-83.
Several human B-cell hybridomas produced by fusion with the mouse X human partner (SHM-D33), and previously assessed for stability of human monoclonal antibody production, have now been assessed for (1) presence of structural genes coding for human immunoglobulin, (2) amount of human DNA, and (3) the rate of loss of human DNA. We found that the proportion of human DNA in clonal populations derived from parental hybridoma populations was extremely variable. Human DNA content varied from 20% to 50% in antibody-producing hybridoma clones. However, loss of antibody production is accompanied by loss of structural immunoglobulin genes and an accelerated loss of greater than 95% of the human component of the hybridoma DNA. In one hybridoma clone, the measured rate of depletion of cellular human DNA was dramatically increased soon after loss of antibody production. These data suggest that stability of human antibody production in hybridomas is dependent on the ability of hybridomas to retain human DNA, and that there is clonal heterogeneity with respect to this ability within hybridoma populations.
几个通过与小鼠X人融合伙伴（SHM-D33）融合产生的人B细胞杂交瘤，之前已对其产生人单克隆抗体的稳定性进行了评估，现在又对其进行了以下评估：（1）编码人免疫球蛋白的结构基因的存在情况，（2）人DNA的含量，以及（3）人DNA的丢失率。我们发现，源自亲本杂交瘤群体的克隆群体中人DNA的比例变化极大。在产生抗体的杂交瘤克隆中，人DNA含量在20%至50%之间变化。然而，抗体产生的丧失伴随着结构免疫球蛋白基因的丧失以及杂交瘤DNA中超过95%的人成分的加速丧失。在一个杂交瘤克隆中，抗体产生丧失后不久，细胞中人DNA的消耗速率显著增加。这些数据表明，杂交瘤中人抗体产生的稳定性取决于杂交瘤保留人DNA的能力，并且在杂交瘤群体中，就这种能力而言存在克隆异质性。
