Wykes M, Poudrier J, Lindstedt R, Gray D
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, GB.
Eur J Immunol. 1998 Feb;28(2):548-59. doi: 10.1002/(SICI)1521-4141(199802)28:02<548::AID-IMMU548>3.0.CO;2-2.
CD40 and CD40 ligand (CD40L) form one of most important receptor-ligand pairs that dock during T-B cell interactions as part of T-dependent antibody responses. It has been reported that among other cell types, B cells can express CD40L. Here we show that a large proportion of mouse B cells express CD40L in their cytoplasm, but not on the surface and that this is readily released as a soluble molecule. Thus, in their resting state up to 50% of mouse B cells express CD40L within their cytoplasm and both the proportion of cells expressing and the amount of CD40L is increased by signaling through immunoglobulin (Ig) or CD38. In contrast, T cell-derived signals such as CD40L (anti-CD40) or Th2-type cytokines cause a decrease in CD40L expression that is related to a release of a soluble form of the molecule from the cell. Supernatants from B cells activated with anti-Ig and anti-CD40 contain CD40L in a variety of forms (18 kDa, 33 kDa and 66 kDa) that are readily detectable by immunoprecipitation with CD40-Fc gamma fusion protein (CD40-Ig) followed by Western blotting with anti-CD40L antibody (MR1). The 33-kDa species is distinct from the 39-kDa membrane-bound molecule found in activated T cells or in resting B cells and appears to be a novel soluble form of CD40L. Inhibition of T cell-independent in vitro stimulation of B cells with CD40-Ig or anti-CD40L suggests that the B cell-derived soluble CD40L or CD40L expressed on the B cell surface can play a positive role in B cell proliferation.
CD40与CD40配体（CD40L）形成了最重要的受体-配体对之一，作为T细胞依赖性抗体反应的一部分，在T-B细胞相互作用过程中结合。据报道，在其他细胞类型中，B细胞可以表达CD40L。在此我们表明，很大一部分小鼠B细胞在其细胞质中表达CD40L，但不在表面表达，并且这一分子很容易作为可溶性分子释放出来。因此，在静息状态下，高达50%的小鼠B细胞在其细胞质中表达CD40L，并且通过免疫球蛋白（Ig）或CD38发出信号可增加表达CD40L的细胞比例以及CD40L的量。相比之下，T细胞衍生的信号，如CD40L（抗CD40）或Th2型细胞因子会导致CD40L表达减少，这与该分子的可溶性形式从细胞中释放有关。用抗Ig和抗CD40激活的B细胞的上清液含有多种形式（18 kDa、33 kDa和66 kDa）的CD40L，通过用CD40-Fcγ融合蛋白（CD40-Ig）进行免疫沉淀，随后用抗CD40L抗体（MR1）进行蛋白质印迹很容易检测到这些形式。33-kDa的形式与在活化T细胞或静息B细胞中发现的39-kDa膜结合分子不同，似乎是CD40L的一种新型可溶性形式。用CD40-Ig或抗CD40L抑制B细胞的T细胞非依赖性体外刺激表明，B细胞衍生的可溶性CD40L或B细胞表面表达的CD40L在B细胞增殖中可发挥积极作用。
