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gaoshandian1金虫 (小有名气)
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在黏膜中通过提供长命浆细胞维持长期体液免疫
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Falk Hiepe , Andreas Radbruch The biology of antibody-secreting cells is still a matter of controversial discussion, more than 60 years after the original observation of plasma cells by Astrid Fagraeus [1]. One of the key questions is how the migration and lifespan of antibody-secreting cells is linked to their generation? Plasma cells generated in secondary systemic immune responses can migrate from spleen and lymph nodes to the bone marrow, and a fraction of them will be long-lived, surviving in dedicated plasma cell survival niches. These long-lived plasma cells constitute a humoral memory on their own, independent of the reactive memory of memory B cells [2], [3]. But how about antibody-secreting cells of mucosal immune responses, which contribute a significant proportion of serum antibodies and most of the secretory IgA [4]? Little is known about their migration and lifespan. There are some indications of long-lasting antibody production in nasal-mucosa-associated lymphoid tissues (NALT). A few years ago, Hou and colleagues [5] analysed the specific antibody responses in NALT following experimental nasal influenza infection of mice. They determined, by ELISPOT, long-term virus-specific antibody secretion which lasted for the life of the animals. Furthermore, there were differences between the anatomical sites of NALT regarding the frequency of specific plasma cells and the duration of the immune response. Unlike organized NALT (O-NALT), the diffuse NALT (D-NALT) emerged as the site of virus-specific plasma cells [5]. In this issue of the European Journal of Immunology, the same group now shows that intranasal immunization with inactivated respiratory syncytial virus (RSV) in combination with bacterial outer membrane vesicles, a component which serves as an efficient adjuvant, can generate a population of RSV-specific plasma cells that provides long-term protection against subsequent RSV infections [6]. Are these plasma cells short-lived and continuously generated in a chronic immune reaction [7], [8] or are they long-lived "memory" plasma cells [2], [8]-[11]? An argument in favour of the chronic immune reaction is the requirement for a potent adjuvant, which in all likelihood not only potentiates but also prolongs the immune reaction. An argument in favour of the longevity of the mucosal plasma cells generated is the finding that the specific plasma cells are initially detected both in O-NALT and D-NALT, but only in D-NALT at later time points. So far, it has been shown that plasmablasts generated in mucosal immune responses express the chemokine receptor CCR9 [12], and are attracted by CCL25, a mucosal chemokine, unlike plasmablasts generated in systemic immune responses [13]. The question whether or not the mucosal tissue provides survival niches for long-lived plasma cells, like inflamed tissue [14] and bone marrow [15], is still open. It will be a challenge for future work to determine whether or not antibody-secreting cells are long-lived, when generated in mucosal immune responses like those described in the current study [6] by Hou and colleagues, and located in the mucosa. It will also be of interest to determine whether or not plasmablasts generated in mucosal immune responses do migrate to the bone marrow and enter the pool of long-lived plasma cells there. The answer to these questions is of considerable practical relevance with respect to the stability of protection provided by systemic versus mucosal vaccination over the years, and the prospective therapeutic impact of immunosuppression on humoral mucosal immunity and autoimmunity and type I allergic reactions to inhaled antigens. --------------- European Journal of Immunology Volume 36, Issue 5, Pages 1068-1069 相关链接 |
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