Conge A M, Tarte K, Reynes J, Segondy M, Gerfaux J, Zembala M, Vendrell J P
Centre National Recherche Scientifique, Laboratoire d'Immunologie des Infections Retrovirales, Institut de Biologie, Montpellier, France.
AIDS. 1998 Aug 20;12(12):1437-49. doi: 10.1097/00002030-199812000-00005.
This study was performed to investigate the hyporeactivity of purified B lymphocytes from HIV-1-infected patients.
Given the importance of the B-cell Ag receptor (BCR) and CD40 in B-lymphocyte activation, we assessed the capacity of purified peripheral blood B lymphocytes from HIV-1-infected patients to differentiate into Ig-secreting cells in a T-cell- and accessory-cell-independent system of BCR and CD40 costimulation.
B lymphocytes from 21 HIV-1-infected patients were purified by immunomagnetic cell separation and costimulated with immobilized anti-CD40 monoclonal antibodies and Staphylococcus aureus Cowan I particles in the presence of interleukin (IL)-2 and IL-10. Homotypic aggregate formation, apoptosis, cell cycle entrance, proliferation and Ig secretion of B cells were analysed.
Costimulation by the BCR and CD40 induced proliferation and differentiation of B lymphocytes into Ig-secreting cells in 13 patients (group I) but not in eight patients (group II). For three patients in group II, the dual triggering induced apoptosis of B cells. The unexpected inability of these cells to differentiate was associated with a high CD38 expression and a weak spontaneous production of Ig or anti-HIV-1 antibodies in patients with a high viral load and a low CD4+ lymphocyte count. Despite this anomaly, the B cells from group II were able to progress through the cell cycle after stimulation with a combination of phorbol ester and ionomycin in complete medium, suggesting an impairment in BCR and CD40 early signal transduction.
Intrinsic in vitro hyporeactivity of B lymphocytes to dual triggering of BCR and CD40 was observed in advanced HIV-1 disease and appeared to be related to in vivo hyperactivation of B cells.
本研究旨在调查来自HIV-1感染患者的纯化B淋巴细胞的低反应性。
鉴于B细胞抗原受体（BCR）和CD40在B淋巴细胞活化中的重要性，我们评估了来自HIV-1感染患者的纯化外周血B淋巴细胞在BCR和CD40共刺激的T细胞和辅助细胞非依赖性系统中分化为分泌Ig细胞的能力。
通过免疫磁珠细胞分离法纯化21例HIV-1感染患者的B淋巴细胞，并在白细胞介素（IL）-2和IL-10存在的情况下，用固定化抗CD40单克隆抗体和金黄色葡萄球菌Cowan I颗粒进行共刺激。分析B细胞的同型聚集形成、凋亡、细胞周期进入、增殖和Ig分泌。
BCR和CD40的共刺激在13例患者（I组）中诱导B淋巴细胞增殖并分化为分泌Ig的细胞，但在8例患者（II组）中未诱导。对于II组中的3例患者，双重触发诱导B细胞凋亡。这些细胞意外无法分化与高病毒载量和低CD4 +淋巴细胞计数患者中高CD38表达以及Ig或抗HIV-1抗体的弱自发产生有关。尽管存在这种异常，但II组的B细胞在完全培养基中用佛波酯和离子霉素组合刺激后能够进入细胞周期，这表明BCR和CD40早期信号转导存在缺陷。
在晚期HIV-1疾病中观察到B淋巴细胞对BCR和CD40双重触发的内在体外低反应性，并且似乎与B细胞的体内过度活化有关。
