Ambrus J L, Haneiwich S, Chesky L, McFarland P, Peters M G, Engler R J
Department of Medicine, Jewish Hospital of St. Louis, Washington University School of Medicine, St. Louis, Mo.
J Allergy Clin Immunol. 1991 Jun;87(6):1138-49. doi: 10.1016/0091-6749(91)92160-3.
Patients with common variable immunodeficiency (CVI) generally fail to produce antigen-specific IgG. We have identified a lymphokine called high molecular weight B cell growth factor (HMW BCGF) that expands an IgG-producing subpopulation of B cells. The B cells from 15 of 16 patients with CVI evaluated in this study failed to proliferate to HMW BCGF, although they proliferated normally to another BCGF, low molecular weight BCGF (LMW BCGF). Nevertheless, 11 patients had more than normal numbers of B cells expressing HMW BCGF receptors. The HMW BCGF receptors on the B cells of three patients with CVI studied were the same molecular weight as the normal HMW BCGF receptor. Examination of B cells from four patients with CVI for intracellular signals produced in normal B cells after stimulation with HMW BCGF revealed that B cells from patients with CVI failed to developed significant increases in cyclic adenosine monophosphate or phosphoinositides after HMW BCGF stimulation. However, cytoplasmic phosphoinositides in the B cells from all four patients with CVI were already increased above what is observed in normal B cells before stimulation with HMW BCGF (either freshly isolated or Staphylococcus aureus Cowan I-activated B cell). Thus, the failure of B cells from patients with CVI to respond to HMW BCGF may be related to their abnormal activation in vivo. Since HMW BCGF expands a subpopulation of memory B cells, the inability of CVI B cells to respond to HMW BCGF may contribute to their abnormal secondary responses to antigens.
常见变异型免疫缺陷（CVI）患者通常无法产生抗原特异性IgG。我们已经鉴定出一种名为高分子量B细胞生长因子（HMW BCGF）的淋巴因子，它能使产生IgG的B细胞亚群扩增。在本研究中评估的16例CVI患者中，有15例患者的B细胞尽管对另一种B细胞生长因子——低分子量B细胞生长因子（LMW BCGF）能正常增殖，但对HMW BCGF却无增殖反应。然而，11例患者表达HMW BCGF受体的B细胞数量多于正常水平。对3例CVI患者B细胞上的HMW BCGF受体研究发现，其分子量与正常HMW BCGF受体相同。对4例CVI患者的B细胞在用HMW BCGF刺激后正常B细胞中产生的细胞内信号进行检测，结果显示，CVI患者的B细胞在用HMW BCGF刺激后，环磷酸腺苷或磷酸肌醇并未显著增加。然而，在所有4例CVI患者的B细胞中，在用HMW BCGF刺激之前（无论是新鲜分离的还是经金黄色葡萄球菌Cowan I激活的B细胞），细胞质磷酸肌醇就已经高于正常B细胞中的水平。因此，CVI患者的B细胞对HMW BCGF无反应可能与其在体内的异常激活有关。由于HMW BCGF能使记忆B细胞亚群扩增，CVI B细胞对HMW BCGF无反应可能导致其对抗原的二次反应异常。
