Vajdy M, Lycke N
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Immunology. 1995 Nov;86(3):336-42.
In recent studies we have demonstrated that immunological B- and T-cell memory may be stimulated effectively by oral immunization, simply by admixing protein antigens with cholera toxin (CT) adjuvant. Here we extend information by employing a hapten-carrier system allowing us to separate B- and T-cell memory and to evaluate the requirement of memory T cells for effective reactivation of mucosal memory B cells. We found that 2 weeks following oral priming immunizations with dinitrophenyl-keyhole limpet haemocyanin (DNP-KLH) plus CT adjuvant, significant serum anti-DNP antibodies of IgG, IgA and IgM immunoglobulin classes were demonstrated. However, after 2 years only IgM anti-DNP antibodies could still be detected in serum. When memory lymphocytes were isolated from these mice, from both systemic and gut-associated lymphoid tissues, and challenged with antigen in vitro, vigorous IgM, but no IgG or IgA, anti-DNP production was observed. By contrast, when the DNP-KHL-primed memory mice were challenged in vivo by an oral booster immunization with DNP-KLH plus CT adjuvant, strong systemic IgG and local mucosal IgA anti-DNP responses were recorded, while IgM anti-DNP production was poor. Moreover, the mucosal memory B cells from DNP-KHL-immunized mice were more responsive in vivo to an oral booster immunization with the carrier-specific antigen, DNP-KLH, compared to that provided by an unrelated carrier, DNP-human serum albumin (HSA), which gave only poor mucosal and systemic anti-DNP B-cell responses. Taken together our data suggest that mucosal memory B cells are recirculating cells that have retained their ability to produce IgM antibodies and, therefore, have not undergone switch differentiation involving gene rearrangements with constant mu-chain deletions. Furthermore, mucosal B-cell memory and CD4+ T-cell memory are closely interconnected phenomena, requiring both components for effective expression and probably also for maintenance of immunological memory in the mucosal immune system.
在最近的研究中，我们已经证明，通过口服免疫，简单地将蛋白质抗原与霍乱毒素（CT）佐剂混合，可有效刺激免疫性B细胞和T细胞记忆。在此，我们通过采用半抗原-载体系统扩展了相关信息，该系统使我们能够分离B细胞和T细胞记忆，并评估记忆T细胞对粘膜记忆B细胞有效再激活的需求。我们发现，在用二硝基苯基-钥孔戚血蓝蛋白（DNP-KLH）加CT佐剂进行口服初次免疫后2周，血清中出现了显著的IgG、IgA和IgM免疫球蛋白类别的抗DNP抗体。然而，2年后，血清中仅能检测到IgM抗DNP抗体。当从这些小鼠的全身和肠道相关淋巴组织中分离记忆淋巴细胞，并在体外进行抗原刺激时，观察到强烈的IgM抗DNP产生，但没有IgG或IgA产生。相比之下，当用DNP-KLH加CT佐剂对经DNP-KHL初次免疫的记忆小鼠进行口服加强免疫时，记录到强烈的全身IgG和局部粘膜IgA抗DNP反应，而IgM抗DNP产生较少。此外，与无关载体DNP-人血清白蛋白（HSA）相比，经DNP-KHL免疫的小鼠的粘膜记忆B细胞在体内对载体特异性抗原DNP-KLH的口服加强免疫反应更强，后者仅产生较弱的粘膜和全身抗DNP B细胞反应。综合我们的数据表明，粘膜记忆B细胞是循环细胞，保留了产生IgM抗体的能力，因此，尚未经历涉及恒定μ链缺失的基因重排的类别转换分化。此外，粘膜B细胞记忆和CD4+ T细胞记忆是密切相关的现象，粘膜免疫系统中有效的表达以及可能的免疫记忆维持都需要这两个成分。
