Jelinek D F
Department of Immunology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, Minnesota 55905, USA.
Ann Allergy Asthma Immunol. 2000 Apr;84(4):375-85; quiz 385-7. doi: 10.1016/S1081-1206(10)62267-3.
Type I hypersensitivity reactions uniquely involve the IgE class of immunoglobulins (Ig). IgE differs from other classes of Ig in that the majority of the antibodies are bound to high affinity IgE Fc(epsilon)Rs that are expressed on a variety of cell types. Some of these cell types, most notably, mast cells and basophils, are triggered to undergo rapid activation, degranulation, and release of bioactive mediators following binding of antigen to Fc(epsilon)RI-bound IgE. Because of the central role that IgE antibodies and these mediators play in the tissue injury typical of type I hypersensitivity, this article will review the various stages of B lymphocyte development, activation, and differentiation and comment, where appropriate on potential sites of deregulation in allergic disease.
A literature search of the stages of B lymphocyte differentiation with emphasis on events that concern IgE expression was performed.
B lymphocyte differentiation into IgE expressing cells is dependent upon three types of signals. The first signal is delivered through the B cell antigen receptor and is pivotal in determining the antigenic specificity of the response. The second signal is provided primarily by cytokines derived from T helper 2 (TH2) cells, ie, interleukin (IL)-4 and IL-13. These cytokines are under tight regulation and their role appears to be the stimulation of transcription through the Ig constant region genes. Finally, the third signal is provided via the interaction between the constitutively expressed CD40 molecule on B lymphocytes and CD154 (CD40 ligand), a molecule expressed on T lymphocytes following activation. Elevated levels of IgE in atopic individuals may result from the preferential activation of TH2 cells.
A greater understanding of the regulation of IgE expression may be central to the development of more effective immunotherapy strategies designed to attenuate IgE synthesis.
I型超敏反应独特地涉及免疫球蛋白（Ig）的IgE类别。IgE与其他Ig类别不同，在于大多数抗体与在多种细胞类型上表达的高亲和力IgE Fc（ε）受体结合。其中一些细胞类型，最显著的是肥大细胞和嗜碱性粒细胞，在抗原与Fc（ε）RI结合的IgE结合后，会被触发进行快速激活、脱颗粒并释放生物活性介质。由于IgE抗体和这些介质在I型超敏反应典型的组织损伤中起核心作用，本文将综述B淋巴细胞发育、激活和分化的各个阶段，并在适当之处对过敏性疾病中失调的潜在位点进行评论。
进行了一项关于B淋巴细胞分化阶段的文献检索，重点关注与IgE表达相关的事件。
B淋巴细胞分化为表达IgE的细胞取决于三种信号。第一个信号通过B细胞抗原受体传递，对于确定反应的抗原特异性至关重要。第二个信号主要由源自辅助性T细胞2（TH2）的细胞因子提供，即白细胞介素（IL）-4和IL-13。这些细胞因子受到严格调控，其作用似乎是通过Ig恒定区基因刺激转录。最后，第三个信号通过B淋巴细胞上组成性表达的CD40分子与CD154（CD40配体）之间的相互作用提供，CD154是T淋巴细胞激活后表达的一种分子。特应性个体中IgE水平升高可能是由于TH2细胞的优先激活。
更深入了解IgE表达的调控可能是开发更有效的免疫治疗策略以减弱IgE合成的核心。
