Le Gros G, Schultze N, Walti S, Einsle K, Finkelman F, Kosco-Vilbois M H, Heusser C
Department of Asthma/Allergy, Pharma Research, Ciba, Basel, Switzerland.
Eur J Immunol. 1996 Dec;26(12):3042-7. doi: 10.1002/eji.1830261233.
We studied whether long-lived IgE+ memory B cells develop following three types of primary IgE immune responses. Immunization of mice with anti-IgD antibody induced a T cell-dependent, interleukin (IL)-4-dependent primary IgE response and the formation of IgE isotype switched (IgE+) memory B cells. These IgE+ memory B cells could be stimulated in vivo by injection with goat anti-IgE antibodies to produce a profound IL-4-independent memory IgE response. By contrast, both infection of mice with Nippostrongylus brasiliensis or repeated immunization with benzylpenicilloyl-keyhole limpet hemocyanin (BPO-KLH) in alum stimulated good primary IgE responses and profound memory T cell-dependent antigen-specific IgE responses, but failed to induce the development of long lived IgE+ memory B cells because they could not be recalled with goat anti-IgE antibodies. Mice receiving double immunizations combining anti-IgD with either N. brasiliensis infection or BPO-KLH immunization mounted significant goat anti-IgE-induced secondary IgE responses, but no N. brasiliensis or BPO-KLH-specific IgE could be detected. This indicates that the N. brasiliensis and BPO-KLH induced immune responses do not suppress the development of IgE+ B cells, but rather, do not provide the necessary conditions for their formation. Taken together these data indicate that long-lived IgE+ B cells fail to develop during the primary IgE response to N. brasiliensis infection or BPO-KLH immunization. By contrast, significant numbers of IgE+ memory B cells form during the primary IgE immune response induced by anti-IgD immunization. Our observations suggest that immunization protocols involving membrane IgD cross-linking and limited duration of cognate T cell help are necessary for the formation of IgE+ memory B cells. It will be important to determine the relevance of membrane IgD interaction with allergens, as this would influence the design of new therapies for the treatment of allergy and asthma.
我们研究了在三种类型的原发性IgE免疫反应后，长寿的IgE⁺记忆B细胞是否会发育。用抗IgD抗体免疫小鼠可诱导T细胞依赖性、白细胞介素（IL）-4依赖性原发性IgE反应以及IgE同种型转换（IgE⁺）记忆B细胞的形成。这些IgE⁺记忆B细胞可通过注射山羊抗IgE抗体在体内被刺激，以产生强烈的不依赖IL-4的记忆性IgE反应。相比之下，用巴西日圆线虫感染小鼠或在明矾中用苄青霉素酰基-钥孔戚血蓝蛋白（BPO-KLH）重复免疫，均可刺激良好的原发性IgE反应和强烈的记忆性T细胞依赖性抗原特异性IgE反应，但未能诱导长寿的IgE⁺记忆B细胞的发育，因为它们不能被山羊抗IgE抗体召回。接受抗IgD与巴西日圆线虫感染或BPO-KLH免疫联合双重免疫的小鼠产生了显著的山羊抗IgE诱导的继发性IgE反应，但未检测到巴西日圆线虫或BPO-KLH特异性IgE。这表明巴西日圆线虫和BPO-KLH诱导的免疫反应不会抑制IgE⁺B细胞的发育，而是没有为其形成提供必要条件。综合这些数据表明，在对巴西日圆线虫感染或BPO-KLH免疫的原发性IgE反应期间，长寿的IgE⁺B细胞无法发育。相比之下，在抗IgD免疫诱导的原发性IgE免疫反应期间，会形成大量的IgE⁺记忆B细胞。我们的观察结果表明，涉及膜IgD交联和同源T细胞辅助有限持续时间的免疫方案对于IgE⁺记忆B细胞的形成是必要的。确定膜IgD与变应原相互作用的相关性将很重要，因为这会影响治疗过敏和哮喘的新疗法的设计。
