Law C L, Wörmann B, LeBien T W
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Leukemia. 1990 Nov;4(11):732-8.
CD40 was originally identified on circulating and tonsillar human B cells, and anti-CD40 monoclonal antibodies (MoAb) are known to deliver a progression signal to activated B cells. However, the expression and function of CD40 on human B cell precursors (BCP) have not been examined in detail. Two new anti-CD40 MoAb were produced and shown to recognize an epitope indistinguishable from the anti-CD40 antibody G28-5. CD40 was readily detected on normal and leukemic BCP by flow cytometry, and cell surface expression was upregulated by phorbol ester. Despite the ability of normal and leukemic BCP to respond to phorbol ester (PMA) and/or low molecular weight B cell growth factor (L-BCGF), anti-CD40 exerted no stimulatory action and could not enhance the response of these cells to PMA, L-BCGF, or both. Cross-linking anti-CD40 MoAb with rabbit anti-mouse Ig also failed to induce a proliferative response in normal BCP. We conclude that anti-CD40 does not exert demonstrable agonistic effects on normal and leukemic human BCP. Our results suggest that signal delivery through CD40 and/or subsequent intracellular signal processing may require accessory molecules not expressed in BCP, or CD40 may subserve a different function for BCP.
CD40最初是在循环的和扁桃体的人B细胞上被鉴定出来的，已知抗CD40单克隆抗体（MoAb）能向活化的B细胞传递一个增殖信号。然而，CD40在人B细胞前体（BCP）上的表达和功能尚未得到详细研究。制备了两种新的抗CD40 MoAb，并显示它们识别的表位与抗CD40抗体G28-5无法区分。通过流式细胞术很容易在正常和白血病BCP上检测到CD40，佛波酯可上调细胞表面表达。尽管正常和白血病BCP有能力对佛波酯（PMA）和/或低分子量B细胞生长因子（L-BCGF）作出反应，但抗CD40没有发挥刺激作用，也不能增强这些细胞对PMA、L-BCGF或两者的反应。用兔抗小鼠Ig交联抗CD40 MoAb也未能在正常BCP中诱导增殖反应。我们得出结论，抗CD40对正常和白血病的人BCP没有明显的激动作用。我们的结果表明，通过CD40传递信号和/或随后的细胞内信号处理可能需要BCP中未表达的辅助分子，或者CD40可能对BCP具有不同的功能。
