Etiology of congenital agammaglobulinemia: Growth defect of precursor B lymphoblastoid cell lines and immunoglobulin gene rearrangements.

先天性无丙种球蛋白血症的病因：前体 B 淋巴母细胞系的生长缺陷和免疫球蛋白基因重排。

基本信息

批准号：
62480224
负责人：
TSUCHIYA Shigeru
金额：
$ 3.97万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Epstein-Barr virus (EBV) induced B lymphoblastoid cell lines (B-LCL) were established from bone marrow cells of the patients with congenital agammaglobulinemia (CAG).We found several immature B-LCL, some of which possess no cell-surface and cytoplastic immunoglobulins, or possess only cytoplasmic heavy chains. We examined the mode of expression of B-cell associated antigens on EBV-induced B-LCL and failed to detect any CAG specific and developmental stage-specific expression of known B-cell related antigens on those B-LCL. These facts indicate that expression of B cell associated antigens on EBV-induced B-LCL does not depend on the developmental stage of B cells, rather depend on the state of EBV infections.If we can detect LCL which express immunoglobulins with very unusual manner, those LCL will probably give us oppotunities to elucidate the etiology of CAG. Fortunately we found 2 such cell lines, K5 and K4, from the same CAG patient. K5 was very unique because they expressed only IgD (delea,lambda) on the surface and produced IgD. K4 was also very unique because they produced lambda heavy chain, and both kappa and lambda light chains. Cell cloning experiments repeated 3 times definitely confirmed that K4 cells produced both kappa and lambda light chains with single mu chains. The pattern of immunoglobolin production seen on K4 and K5 was probably the first ones in the literature. We are going to clone immunoglobuline genes of K4 and K5, and to elucidate the genetic mechanism of the expression of unusual immunoglobulins.

Epstein-Barr病毒（EBV）诱导的B淋巴母细胞系（B-LCL）是从先天性氨基甘露蛋白血症患者的骨髓细胞中建立的。我们发现了几个不成熟的B-LCL，其中一些没有细胞表面和细胞表面和细胞肿瘤的免疫球蛋白，或者仅具有cytop的cytoplast cytopoplasic cytopopic。我们检查了B细胞相关抗原在EBV诱导的B-LCL上的表达方式，但未能检测到这些B-LCL上已知B细胞相关抗原的任何CAG特异性和发育阶段特异性表达。这些事实表明，B细胞在EBV诱导的B-LCL上与B细胞相关的抗原的表达不取决于B细胞的发育阶段，而是取决于EBV感染的状态。如果我们可以检测到以非常不寻常的方式表达免疫光蛋白的LCL，LCL可能会给我们提供CAG的病学。幸运的是，我们从同一CAG患者发现了2条这样的细胞系K5和K4。 K5非常独特，因为它们仅在表面上表达IgD（drea，lambda）并产生IgD。 K4也非常独特，因为它们生产了Lambda重链，以及Kappa和Lambda轻型连锁店。细胞克隆实验重复了3次，肯定证实了K4细胞与单个MU链产生了Kappa和Lambda光链。在K4和K5上看到的免疫球蛋白产生的模式可能是文献中的第一个。我们将转到K4和K5的克隆免疫球蛋白基因，并阐明异常免疫球蛋白表达的遗传机理。