Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response

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 μ(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 B1a 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 (as 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.

次级免疫应答的加速发展，部分可归因于初次免疫诱导产生的循环抗体将抗原快速递送至淋巴滤泡。本文我们提供证据表明，未免疫小鼠体内存在的非特异性IgM（天然抗体）在初次应答的加速过程中发挥了作用。通过Cre重组酶（Cre recombinase）靶向敲除Ig μ(s)聚腺苷酸化位点，我们得以构建一类小鼠：其表达表面IgM的B细胞数量正常，但完全缺乏血清IgM，同时保留其他免疫球蛋白（Ig）亚型。这些小鼠的B淋巴细胞分布整体正常（尽管腹膜腔B1a亚群略有扩增），但在针对T细胞依赖性抗原产生亲和力成熟的IgG应答时出现显著延迟；然而，其T细胞非依赖性应答则有所增强。上述数据表明，抗原激发前存在的IgM（以及可能在免疫后即刻诱导产生的IgM）可加速初次应答的成熟过程，其机制可能是通过与抗原结合，促进淋巴细胞活化和/或抗原捕获。