Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response
Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response
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DOI：
10.1073/pnas.95.17.10089
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发表时间：
1998-08-18
影响因子：
11.1
通讯作者：
Neuberger, MS
中科院分区：
文献类型：
--
作者：
Ehrenstein, MR;O'Keefe, TL;Neuberger, MS
二次免疫应答的加速发展可能部分归因于初次免疫引起的循环抗体将抗原快速递送至淋巴滤泡。在这里，我们提供的证据表明，非特异性IgM存在于幼稚小鼠（天然抗体）在加速初级反应中发挥作用。通过使用Cre重组酶靶向缺失IG mu（s）多聚腺苷酸化位点允许产生小鼠，所述小鼠虽然具有正常数量的表达表面IgM的B细胞，但完全缺乏血清IgM，同时保留其他IG同种型。这些小鼠保留了广泛正常的B淋巴细胞分布（尽管含有稍微扩大的腹膜Bla亚群），但在对T细胞依赖性抗原的亲和力成熟IgG应答的建立方面表现出实质性延迟，然而，T细胞非依赖性应答增强。数据表明，抗原激发前存在的IgM可能与免疫后立即引发的IgM一样，加速了初次应答的成熟，推测是通过与抗原复合并促进淋巴细胞活化和/或抗原捕获。
Accelerated development of the secondary immune response may be attributable in part to the rapid delivery of antigen to lymphoid follicles by circulating antibody elicited on primary immunization. Here we provide evidence indicating that the nonspecific IgM present in naive mice (natural antibody) plays a role in the acceleration of the primary response. Targeted deletion of the Ig mu(s) polyadenylation site by use of Cre recombinase allowed the creation of mice that, although harboring a normal number of B cells expressing surface IgM, completely lacked serum IgM while retaining the other Ig isotypes. These mice retained a broadly normal B lymphocyte distribution (although containing a somewhat expanded peritoneal Bla subset) but exhibited substantial delays in mounting affinity-matured IgG responses to T cell-dependent antigens, The T cell-independent response, however, was augmented. The data indicate that the IgM present before antigen challenge las well, possibly, as that elicited immediately after immunization) accelerates maturation of the primary response, presumably by complexing with the antigen and facilitating lymphocyte activation and/or antigen trapping.