Mori S, Kondo N, Motoyoshi F, Kaneko H, Inoue Y, Orii T
Department of Pediatrics, Gifu University School of Medicine, Japan.
Eur J Immunogenet. 1992 Oct;19(5):273-85. doi: 10.1111/j.1744-313x.1992.tb00070.x.
Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage.
对6例异质性常见变异型免疫缺陷（CVID）患者的种系DNA、DNA重排及免疫球蛋白（Ig）基因的RNA表达进行分析，采用适当探针通过Southern印迹或Northern印迹法检测。用Cμ和Cγ探针杂交中性粒细胞DNA，未检测到多态性。3例患者血清Ig和Ig阳性细胞均几乎未检测到，通过Northern杂交法，未检测到μ mRNA、γ mRNA、α mRNA及κ mRNA。然而，这3例患者的1株爱泼斯坦-巴尔病毒转化的B淋巴母细胞系（LCL）在JH、Cγ和Cκ区域与种系不同，且μ mRNA表达水平较高。这3例患者的B细胞缺陷处于与X连锁无丙种球蛋白血症（XLA）相似的B细胞成熟阶段。6例CVID患者中的另外2例，血清IgM和IgM阳性细胞有一定程度的检测，通过Northern杂交，μ mRNA检测水平较低，但未检测到γ mRNA、α mRNA及κ mRNA。这2例患者的1株LCL可正常表达μ mRNA。最后1例患者，血清IgM正常，血清IgG和IgA略低，Ig阳性细胞正常，μ mRNA和κ mRNA检测水平正常，γ mRNA和α mRNA检测水平较低。该患者的缺陷影响类别转换阶段。这些结果表明，CVID中的原发性B细胞缺陷发生在几个B细胞分化阶段，可通过Ig基因表达及B细胞库中的克隆多样性程度进行分类。此外，本研究支持CVID缺陷与更广泛的细胞功能相关的观点，如调节B淋巴细胞系细胞的增殖和/或克隆扩增。
