Hauke G, Hadam M, Epplen J T, Gahr M, Hollmann A, Peter H H
Abteilung für Rheumatologie und Klinische Immunologie der Medizinischen Universitäts-Klinik, Freiburg.
Immunobiology. 1989 Feb;178(4-5):449-61. doi: 10.1016/S0171-2985(89)80065-8.
The majority of common variable immunodeficiencies (CVID) is caused by intrinsic B cell defects which impede distinct stages of B cell differentiation. B cell differentiation is accompanied by the rearrangement of immunoglobulin (Ig) genes. The first step in the rearrangement process is the assembly of IgH genes, and subsequently, IgL genes are rearranged. During B cell maturation, Ig genes are demethylated in a stepwise, locus-specific manner. Here, we examined the Ig gene rearrangements of four patients with classical CVID and of one child suffering from an unusual immunodeficiency associated with CD5+ B cell lymphocytosis. In one of the four adult patients with CVID, we observed a predominant type of VHDJH-gene rearrangement. In the child, different polyclonal VHDJH-gene rearrangements were found together with a predominant type of kappa light chain gene rearrangement. The rearranged kappa chain genes were methylated (as in the pre-B cell stage). These findings together with the cell phenotype analysis and the clinical course of the disease in the child suggests that in some patients with primary immunodeficiency a maturation arrest may occur in B cells leading to a predominant Ig V gene rearrangement.
大多数常见可变免疫缺陷（CVID）是由内在B细胞缺陷引起的，这些缺陷阻碍了B细胞分化的不同阶段。B细胞分化伴随着免疫球蛋白（Ig）基因的重排。重排过程的第一步是IgH基因的组装，随后，IgL基因进行重排。在B细胞成熟过程中，Ig基因以逐步的、位点特异性的方式去甲基化。在此，我们检测了4例经典CVID患者和1例患有与CD5+B细胞淋巴细胞增多相关的罕见免疫缺陷儿童的Ig基因重排。在4例成年CVID患者中的1例，我们观察到一种主要类型的VHDJH基因重排。在该儿童中，发现了不同的多克隆VHDJH基因重排以及一种主要类型的κ轻链基因重排。重排的κ链基因发生了甲基化（如在前B细胞阶段）。这些发现连同该儿童的细胞表型分析和疾病临床过程表明，在一些原发性免疫缺陷患者中，B细胞可能发生成熟停滞，导致主要的Ig V基因重排。
