Plasma cell survival in the absence of B cell memory.

Plasma cell survival in the absence of B cell memory.
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DOI:
10.1038/s41467-017-01901-w
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发表时间:
2017-11-24
影响因子:
16.6
通讯作者:
Slifka MK
Slifka MK
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hammarlund E;Thomas A;Amanna IJ;Holden LA;Slayden OD;Park B;Gao L;Slifka MK

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预先存在的血清抗体在疫苗介导的抗感染保护中起重要作用,但免疫记忆的潜在机制尚不清楚。临床研究表明,抗原特异性抗体应答可以维持多年,从而产生了这样的理论,即需要记忆B细胞再活化/分化为浆细胞以维持长期抗体产生。在这里,我们提出了一个长达十年的研究中,我们证明了位点特异性生存的骨髓源性浆细胞和持久的抗体反应,多种病毒和疫苗抗原在恒河猴持续记忆B细胞耗竭后多年。此外,在疫苗接种/BrdU给药后10年内可检测到具有浆细胞形态的BrdU+细胞,表明浆细胞可在不存在细胞分裂的情况下持续较长时间。基于这些结果,长寿命的浆细胞代表了负责长期抗体产生和血清学记忆的关键细胞群体。分泌抗体的浆细胞的长期维持和对记忆B细胞的需求尚不清楚。在这里,作者表明,浆细胞和分泌的抗体是长寿的,并在非人类灵长类动物的记忆B细胞的情况下维持了十年以上。
Pre-existing serum antibodies play an important role in vaccine-mediated protection against infection but the underlying mechanisms of immune memory are unclear. Clinical studies indicate that antigen-specific antibody responses can be maintained for many years, leading to theories that reactivation/differentiation of memory B cells into plasma cells is required to sustain long-term antibody production. Here, we present a decade-long study in which we demonstrate site-specific survival of bone marrow-derived plasma cells and durable antibody responses to multiple virus and vaccine antigens in rhesus macaques for years after sustained memory B cell depletion. Moreover, BrdU+ cells with plasma cell morphology can be detected for 10 years after vaccination/BrdU administration, indicating that plasma cells may persist for a prolonged period of time in the absence of cell division. On the basis of these results, long-lived plasma cells represent a key cell population responsible for long-term antibody production and serological memory. The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.
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