Medina F, Segundo C, Rodríguez C, Brieva J A
Servicio de Immunología, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Eur J Immunol. 1997 Mar;27(3):700-6. doi: 10.1002/eji.1830270319.
CD95 ligation elicits apoptotic signals in many cell systems. This study analyzes the effect of anti-CD95 mAb on human cells capable of spontaneous and high-rate Ig secretion. Such cells have been induced in vivo and represent a highly mature B cell stage. Addition of the anti-CD95 monoclonal antibody (mAb) CH11 to tonsil B cells inhibited 50-60% of their spontaneous Ig secretion. The effect was exerted early in the culture and could be reversed by a pre-treatment with a neutralizing mAb. N-acetyl-D-sphingosine (C2-ceramide), although not a close analog, also reduced Ig secretion to a similar extent. The inclusion of a tetrapeptide inhibitor for certain interleukin-1beta-converting enzyme proteases prevented the inhibitory effect of CH11 mAb on tonsil B cells. B cells capable of spontaneous Ab secretion obtained from blood of recently-immunized volunteers were also inhibited by CH11 mAb and C2-ceramide. In contrast, bone marrow (BM) B cells capable of spontaneous Ig secretion were unaffected by these agents. This CD95 ligation-mediated inhibition of tonsil and blood Ig-secreting B cells could not be reversed by cytokines with demonstrated activity on these B cells. Human mature B cells induced in vivo are identifiable as CD38hi cells. Flow cytometric analysis revealed that a fraction of tonsil CD38hi cells expressed low levels of CD95. Moreover, about 20% of these cells exhibited basal apoptosis, as defined by annexin V binding. This phenomenon was markedly increased by CD95 ligation. On the other hand, BM CD38hi cells showed neither CD95 expression nor CD95-induced annexin V binding. These data suggest that CD95 ligation might play a role in the control of human humoral responses by inducing apoptosis in susceptible mature B cells.
CD95 连接在许多细胞系统中引发凋亡信号。本研究分析了抗 CD95 单克隆抗体（mAb）对能够自发且高速率分泌 Ig 的人类细胞的影响。此类细胞已在体内诱导产生，代表高度成熟的 B 细胞阶段。向扁桃体 B 细胞中添加抗 CD95 单克隆抗体（mAb）CH11 可抑制其 50 - 60%的自发 Ig 分泌。该效应在培养早期发挥作用，并且可通过用中和性 mAb 预处理来逆转。N - 乙酰 - D - 鞘氨醇（C2 - 神经酰胺），尽管不是紧密类似物，也能将 Ig 分泌降低到类似程度。包含针对某些白细胞介素 - 1β转化酶蛋白酶的四肽抑制剂可阻止 CH11 mAb 对扁桃体 B 细胞的抑制作用。从近期免疫志愿者血液中获得的能够自发分泌抗体的 B 细胞也受到 CH11 mAb 和 C2 - 神经酰胺的抑制。相比之下，能够自发分泌 Ig 的骨髓（BM）B 细胞不受这些试剂影响。这种 CD95 连接介导的对扁桃体和血液中分泌 Ig 的 B 细胞的抑制作用不能被对这些 B 细胞具有已证实活性的细胞因子所逆转。体内诱导产生的人类成熟 B 细胞可鉴定为 CD38hi 细胞。流式细胞术分析显示，一部分扁桃体 CD38hi 细胞表达低水平的 CD95。此外，按照膜联蛋白 V 结合定义，这些细胞中约 20%表现出基础凋亡。CD95 连接可使这种现象显著增加。另一方面，BM CD38hi 细胞既不表达 CD95，也不表现出 CD95 诱导的膜联蛋白 V 结合。这些数据表明，CD95 连接可能通过诱导易感成熟 B 细胞凋亡在人类体液反应的控制中发挥作用。
