The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections.
The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections.
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DOI：
10.1371/journal.ppat.1000912
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发表时间：
2010-05-20
期刊：
影响因子：
6.7
通讯作者：
Crompton PD
中科院分区：
文献类型：
--
作者：
Weiss GE;Traore B;Kayentao K;Ongoiba A;Doumbo S;Doumtabe D;Kone Y;Dia S;Guindo A;Traore A;Huang CY;Miura K;Mircetic M;Li S;Baughman A;Narum DL;Miller LH;Doumbo OK;Pierce SK;Crompton PD
对恶性疟原虫（Pf）疟疾的免疫力只有在多年反复感染后才能获得，并且在没有持续寄生虫暴露的情况下迅速减弱。抗体是疟疾免疫的核心，但对B细胞生物学知之甚少，而B细胞生物学是导致不能有效获得Pf特异性体液免疫的基础。这项在马里进行的为期一年的前瞻性研究，对185名2至25岁的人进行了研究，结果表明，在多年的重复Pf暴露中，Pf特异性记忆B细胞和抗体是逐步获得的。急性疟疾后，特异性记忆B细胞和抗体滴度都增加了，然后，在6个月的减少的Pf暴露后，收缩到略高于感染前的水平。这种低效的，逐步扩大的Pf特异性记忆B细胞和长寿命的抗体区室取决于Pf的暴露，而不是年龄，根据比较响应破伤风疫苗接种是有效的和稳定的。这些观察为疟疾免疫延迟获得的细胞基础提供了新的见解。 恶性疟原虫（Plasmodium falciparum，Pf）是一种蚊子传播的寄生虫，每年导致5亿多例疟疾病例，其中100万例导致死亡，主要是非洲儿童。研制有效的疟疾疫苗将是控制和最终消除这一疾病的关键一步。迄今为止，大多数许可的疫苗是针对在单次感染后诱导长寿命保护性抗体的病原体的。相比之下，对疟疾的免疫力只有在反复感染后才能获得。抗体在预防疟疾方面发挥着关键作用，但一些研究表明，针对某些Pf蛋白的抗体产生效率低下，并迅速丢失。负责在人类寿命期间维持抗体的细胞是记忆B细胞和长寿浆细胞。为了确定这些细胞是如何产生和维持对Pf感染的反应，我们在马里的一个地区进行了为期一年的研究，该地区经历了为期六个月的疟疾季节。我们发现记忆B细胞和寄生虫特异性的长寿命抗体是在多年的逐步，逐步的方式产生的，尽管强烈的Pf暴露。这与在同一人口中对破伤风疫苗接种的有效反应形成鲜明对比。这项研究为延迟获得疟疾免疫力提供了新的见解。未来对这些观察结果的细胞和分子基础的研究可能为开发高效疟疾疫苗的战略打开大门。
Immunity to Plasmodium falciparum (Pf) malaria is only acquired after years of repeated infections and wanes rapidly without ongoing parasite exposure. Antibodies are central to malaria immunity, yet little is known about the B-cell biology that underlies the inefficient acquisition of Pf-specific humoral immunity. This year-long prospective study in Mali of 185 individuals aged 2 to 25 years shows that Pf-specific memory B-cells and antibodies are acquired gradually in a stepwise fashion over years of repeated Pf exposure. Both Pf-specific memory B cells and antibody titers increased after acute malaria and then, after six months of decreased Pf exposure, contracted to a point slightly higher than pre-infection levels. This inefficient, stepwise expansion of both the Pf-specific memory B-cell and long-lived antibody compartments depends on Pf exposure rather than age, based on the comparator response to tetanus vaccination that was efficient and stable. These observations lend new insights into the cellular basis of the delayed acquisition of malaria immunity. Plasmodium falciparum (Pf) is a mosquito-borne parasite that causes over 500 million cases of malaria annually, one million of which result in death, primarily among African children. The development of an effective malaria vaccine would be a critical step toward the control and eventual elimination of this disease. To date, most licensed vaccines are for pathogens that induce long-lived protective antibodies after a single infection. In contrast, immunity to malaria is only acquired after repeated infections. Antibodies play a key role in protection from malaria, yet several studies indicate that antibodies against some Pf proteins are generated inefficiently and lost rapidly. The cells that are responsible for the maintenance of antibodies over the human lifespan are memory B-cells and long-lived plasma cells. To determine how these cells are generated and maintained in response to Pf infection, we conducted a year-long study in an area of Mali that experiences a six-month malaria season. We found memory B-cells and long-lived antibodies specific for the parasite were generated in a gradual, step-wise fashion over years despite intense Pf exposure. This contrasts sharply with the efficient response to tetanus vaccination in the same population. This study lends new insights into the delayed acquisition of malaria immunity. Future studies of the cellular and molecular basis of these observations could open the door to strategies for the development of a highly effective malaria vaccine.
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DOI：
10.1084/jem.20062571
发表时间：
2007-09-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Anderson SM;Tomayko MM;Ahuja A;Haberman AM;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
4.4
作者：
Crotty, S;Felgner, P;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
20.3
作者：
Dicko, A;Klion, AD;Miller, LH
通讯作者：
Miller, LH
CBA小鼠中质质体的生发中心结构障碍。
影响因子：
3
作者：
Carvalho, Leonardo J. M.;Ferreira-da-Cruz, Maria F.;Daniel-Ribeiro, Claudio T.;Pelajo-Machado, Marcelo;Lenzi, Henrique L.
通讯作者：
Lenzi, Henrique L.