Gascan H, Aversa G G, Gauchat J F, Van Vlasselaer P, Roncarolo M G, Yssel H, Kehry M, Spits H, De Vries J E
Human Immunology Department, DNAX Research Institute, Palo Alto, CA 94304-1104.
Eur J Immunol. 1992 May;22(5):1133-41. doi: 10.1002/eji.1830220505.
In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma delta+, CD4+ and TcR alpha beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell clones was antigen nonspecific, indicating that the TcR alpha beta/CD3 or TcR gamma delta/CD3 complexes were not involved in these T-B cell interactions. Activated TcR alpha beta+, CD8+, and TcR gamma delta+, CD4-CD8-, or resting CD4+ T cell clones were ineffective. Intact TcR alpha beta+ or TcR gamma delta+, CD4+ T cell clones could be replaced by plasma membrane-enriched fractions isolated from these activated CD4+ T cell clones. In contrast, membranes isolated from resting TcR alpha beta+, CD4+, TcR gamma delta+, CD4+ T cell clones or an Epstein-Barr virus (EBV)-transformed B cell line (EBV-LCL) failed to provide the costimulatory signal that, in addition to IL-4, is required for induction of IgE synthesis. As described for intact CD4+ T cells, CD4+ T cell membranes induced purified surface IgM+ B cells to switch to IgG4- and IgE- but not to IgA-producing cells, excluding the possibility of a preferential outgrowth of IgG4- and IgE-committed B cells. The membrane activity was inhibited by protease or heat treatment. Induction of IgE synthesis by B cells co-cultured with both TcR alpha beta+, CD4+ and TcR gamma delta+, CD4+ T cell clones and membrane preparations of these cells was blocked by anti-class II major histocompatibility complex (MHC) monoclonal antibodies (mAb), whereas various anti-CD4 mAb had differential blocking effects. Murine L cells, or EBV-LCL transfected with CD4 could not replace CD4+ T cell clones. These results indicate that, although CD4 and class II MHC antigens are required for productive CD4+ T cell clone-B cell interactions, an additional signal, provided by a membrane associated (glyco)protein that is induced by activation of both TcR alpha beta and TcR gamma delta, CD4+ T cells, is needed for induction of IgE production in the presence of IL-4.
在本研究中，已证明人B细胞在活化的T细胞受体（TcR）γδ⁺、CD4⁺以及TcRαβ⁺、CD4⁺T细胞克隆和白细胞介素（IL）-4提供的接触介导信号作用下，可被诱导转而产生IgE。这些T细胞克隆提供的信号是非抗原特异性的，这表明TcRαβ/CD3或TcRγδ/CD3复合物未参与这些T - B细胞相互作用。活化的TcRαβ⁺、CD8⁺以及TcRγδ⁺、CD4⁻CD8⁻或静息的CD4⁺T细胞克隆均无效。完整的TcRαβ⁺或TcRγδ⁺、CD4⁺T细胞克隆可被从这些活化的CD4⁺T细胞克隆中分离出的富含质膜的组分所替代。相反，从静息的TcRαβ⁺、CD4⁺、TcRγδ⁺、CD4⁺T细胞克隆或爱泼斯坦 - 巴尔病毒（EBV）转化的B细胞系（EBV - LCL）分离的膜未能提供除IL - 4外诱导IgE合成所需的共刺激信号。如对完整CD4⁺T细胞所描述的那样，CD4⁺T细胞膜诱导纯化的表面IgM⁺B细胞转而产生IgG4⁺和IgE⁺细胞，但不产生IgA⁺细胞，排除了IgG4⁺和IgE⁺定向B细胞优先生长的可能性。膜活性可被蛋白酶或热处理抑制。与TcRαβ⁺、CD4⁺以及TcRγδ⁺、CD4⁺T细胞克隆和这些细胞的膜制剂共培养的B细胞诱导IgE合成被抗II类主要组织相容性复合体（MHC）单克隆抗体（mAb）阻断，而各种抗CD4 mAb具有不同的阻断作用。用CD4转染的鼠L细胞或EBV - LCL不能替代CD4⁺T细胞克隆。这些结果表明，尽管CD4和II类MHC抗原对于有效的CD4⁺T细胞克隆 - B细胞相互作用是必需的，但在IL - 4存在下诱导IgE产生还需要由TcRαβ和TcRγδ、CD4⁺T细胞活化诱导的一种膜相关（糖）蛋白提供的额外信号。
