Storek J, King L, Ferrara S, Marcelo D, Saxon A, Braun J
Department of Medicine, UCLA School of Medicine.
Bone Marrow Transplant. 1994 Nov;14(5):783-90.
Patients undergoing bone marrow transplantation are humorally immunodeficient for one or more years post-transplant. This immunodeficiency could be partially caused by B cell repertoire restriction similar to that observed in ontogeny. To test this idea, the abundance of rearranged genomic segments bearing five variable heavy chain (VH) genes was compared in patients at several timepoints post-transplant and in immunologically normal neonates, infants and adults. The genes evaluated in the study (VH6, VH4-58p2, VH3-56p1, VH3-20p1 and VH3-13-2) were selected from those commonly utilized by fetal B cells. The assay employed quantitative PCR and oligonucleotide hybridization detection under conditions designed to detect relatively unmutated forms of these genes. In blood B cells from early post-transplant (2-5 months) patients, these VH genes were markedly overutilized compared with normal adults. B cells from late post-transplant (6-21 months) patients and from normal neonates and infants also overutilized these genes; however, to a lesser degree than early post-transplant B cells. The data suggest that, as in ontogeny, the B cell repertoire is strikingly restricted to fetal-type VH genes early post-transplant, and may become normal only very late (years) post-transplant.
接受骨髓移植的患者在移植后会出现一年或更长时间的体液免疫缺陷。这种免疫缺陷可能部分是由类似于个体发育过程中观察到的B细胞谱系限制引起的。为了验证这一想法，研究人员比较了移植后几个时间点的患者以及免疫正常的新生儿、婴儿和成年人中携带五个可变重链（VH）基因的重排基因组片段的丰度。该研究中评估的基因（VH6、VH4-58p2、VH3-56p1、VH3-20p1和VH3-13-2）是从胎儿B细胞常用的基因中挑选出来的。该检测采用定量PCR和寡核苷酸杂交检测，检测条件旨在检测这些基因相对未突变的形式。在移植后早期（2-5个月）患者的血液B细胞中，与正常成年人相比，这些VH基因被显著过度利用。移植后晚期（6-21个月）患者以及正常新生儿和婴儿的B细胞也过度利用了这些基因；然而，程度低于移植后早期的B细胞。数据表明，与个体发育一样，移植后早期B细胞谱系明显局限于胎儿型VH基因，可能直到移植后很晚（数年）才会恢复正常。
