Wakai M, Pasley P, Sthoeger Z M, Posnett D N, Brooks R, Hashimoto S, Chiorazzi N
Department of Medicine, North Shore University Hospital, Manhasset, NY 11030.
Hybridoma. 1993 Feb;12(1):25-43. doi: 10.1089/hyb.1993.12.25.
A large battery of anti-CD23 mAb were compared for their epitope specificities and for their abilities to alter both IgE binding to cell-associated CD23 and IgE production in vitro in response to three sets of stimulants. The nine mAb tested can be divided into four families which define four antigenic epitopes (A-D) of CD23. Of these four families, two bind antigenic sites, (A and D) that appear to lie outside the IgE ligand binding site and two bind sites (B and C) that appear to be located within or close to this site, as determined by the abilities of appropriate mAb to alter IgE binding to CD23. The effects that these mAb had on IgE secretion by normal peripheral blood mononuclear cells (PBMNC) varied depending on the stimulant employed to induce IgE production. Interactions with epitope A, which was found to lie outside the ligand binding site and to be made more accessible by binding of mAb to other epitopes, had different effects on IgE production than interactions with the other epitopes. Indeed, mAb binding to this epitope lead to as much as a 10 fold enhancement in IgE biosynthesis induced by IL-4 alone or by IL-4 + hydrocortisone whereas interactions at the other sites resulted in almost complete inhibition of IgE production. In addition, mAb reactive with epitopes B and C had minimal effects on IgE production induced by IL-4 + anti-CD40 mAb whereas interactions at epitope A consistently enhanced IgE production. Finally, no apparent direct correlation was found between the ability of individual anti-CD23 mAb to alter IgE binding to cell-associated CD23 and their ability to modulate IgE production by PBMNC. These studies suggest that IgE binding to cell-associated CD23 does not have a major role in the de novo synthesis of IgE that involves CD23 interactions. In addition, the different effects that binding to epitope A vs B or C have on IgE synthesis suggest that molecular interactions between distinct portions of the CD23 molecule and other cell surface molecules expressed on the same B cell or adjacent communicating cells may lead to divergent cellular effects on IgE production. Finally these studies imply that only epitope A is involved in the generation of an IgE response through the CD40 pathway.
比较了大量抗CD23单克隆抗体（mAb）的表位特异性，以及它们改变IgE与细胞相关CD23结合的能力，和在体外对三组刺激物产生反应时改变IgE产生的能力。所测试的9种单克隆抗体可分为4个家族，它们定义了CD23的4个抗原表位（A - D）。在这4个家族中，有两个结合抗原位点（A和D），这些位点似乎位于IgE配体结合位点之外，另外两个结合位点（B和C）似乎位于该位点内或靠近该位点，这是通过适当单克隆抗体改变IgE与CD23结合的能力来确定的。这些单克隆抗体对正常外周血单个核细胞（PBMNC）分泌IgE的影响因用于诱导IgE产生的刺激物而异。与表位A的相互作用，该表位位于配体结合位点之外，并且通过单克隆抗体与其他表位的结合使其更易接近，与其他表位的相互作用相比，对IgE产生有不同的影响。实际上，与该表位结合的单克隆抗体导致单独的IL - 4或IL - 4 +氢化可的松诱导的IgE生物合成增强多达10倍，而在其他位点的相互作用导致IgE产生几乎完全受到抑制。此外，与表位B和C反应的单克隆抗体对IL - 4 +抗CD40单克隆抗体诱导的IgE产生影响最小，而在表位A的相互作用始终增强IgE产生。最后，未发现单个抗CD23单克隆抗体改变IgE与细胞相关CD23结合的能力与其调节PBMNC产生IgE的能力之间存在明显的直接相关性。这些研究表明，IgE与细胞相关CD23的结合在涉及CD23相互作用的IgE从头合成中不起主要作用。此外，与表位A与B或C的结合对IgE合成的不同影响表明，CD23分子不同部分与同一B细胞或相邻通讯细胞上表达的其他细胞表面分子之间的分子相互作用可能导致对IgE产生的不同细胞效应。最后，这些研究表明只有表位A通过CD40途径参与IgE反应的产生。
