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

从先天性无丙种球蛋白血症（CAG）患者的骨髓细胞中建立了EB病毒（EBV）诱导的B类淋巴母细胞系（B-LCL），发现了几种不成熟的B-LCL，其中有些不具有细胞表面和胞质免疫球蛋白，或仅具有胞浆重链。我们检查了EBV诱导的B-LCL上B细胞相关抗原的表达模式，并且未能检测到这些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细胞相关抗原的表达与B细胞的发育阶段无关，而与EBV感染的状态有关，如果能检测到异常表达免疫球蛋白的LCL，将为阐明CAG的病因提供可能。幸运的是，我们从同一个CAG患者中发现了两个这样的细胞系，K5和K4。K5是非常独特的，因为它们在表面上仅表达IgD（delea，lambda）并产生IgD。K4也非常独特，因为它们产生λ重链，以及κ和λ轻链。重复3次的细胞克隆实验明确证实，K4细胞产生具有单个μ链的κ和λ轻链。在K4和K5上观察到的免疫球蛋白产生模式可能是文献中的第一个。我们将克隆K4和K5的免疫球蛋白基因，并阐明异常免疫球蛋白表达的遗传机制。

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.