National Institute for Medical Research, Tanga Research Centre, Amani Biomedical Research Laboratory, Tanga, Tanzania.
Infect Immun. 2012 Feb;80(2):633-42. doi: 10.1128/IAI.05188-11. Epub 2011 Nov 21.
The 19-kDa carboxyl-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) has been shown to regulate antibody (Ab)-mediated protective immunity to blood-stage malaria infection. But the serological memory to this antigen tends to be short-lived, and little is known of the mechanisms that regulate the formation of B cell memory to MSP-1(19) antigen. We studied the formation of B cell memory response after immunization with the recombinant 19-kDa Plasmodium falciparum merozoite surface protein 1 (PfMSP-1(19)). Immunization with PfMSP-1(19) resulted in delayed increase in germinal center (GC) B cell numbers. This poor GC reaction correlated with short-lived PfMSP-1(19)-specific antibodies in serum and the short life of PfMSP-1(19)-specific plasma cells and memory B cells (MBCs) in spleen and bone marrow. PfMSP-1(19)-specific MBCs were capable of producing antigen (Ag)-specific Ab-secreting cell (ASC) responses that were short-lived following challenge immunization of the immune mice with antigen or transgenic Plasmodium berghei parasite expressing PfMSP-1(19) in place of native P. berghei MSP-1(19) at 8 weeks after the last immunization or following adoptive transfer into naive hosts. However, no protection was achieved in PfMSP-1(19) immune mice or recipient mice with PfMSP-1(19)-specific MBCs following challenge with transgenic P. berghei. Our findings suggest that PfMSP-1(19)-specific IgG production by short-lived plasma cells combined with the poor ability of the PfMSP-1(19)-induced MBCs to maintain the anamnestic IgG responses failed to contribute to protection against infection.
疟原虫裂殖子表面蛋白 1（MSP-1（19））的 19kDa 羧基末端片段已被证明可调节抗体（Ab）介导的抗血期疟原虫感染的保护性免疫。但是，针对这种抗原的血清记忆往往是短暂的，并且对于调节针对 MSP-1（19）抗原的 B 细胞记忆形成的机制知之甚少。我们研究了用重组恶性疟原虫裂殖子表面蛋白 1（PfMSP-1（19））免疫后 B 细胞记忆反应的形成。PfMSP-1（19）免疫导致生发中心（GC）B 细胞数量的延迟增加。这种较差的 GC 反应与血清中短暂的 PfMSP-1（19）特异性抗体以及脾脏和骨髓中 PfMSP-1（19）特异性浆细胞和记忆 B 细胞（MBC）的短暂寿命相关。PfMSP-1（19）特异性 MBC 能够产生抗原（Ag）特异性 Ab 分泌细胞（ASC）反应，在最后一次免疫后 8 周用抗原或表达 PfMSP-1（19）的转基因伯氏疟原虫寄生虫对免疫小鼠进行挑战免疫或通过过继转移到幼稚宿主后，这些反应是短暂的。然而，在 PfMSP-1（19）免疫小鼠或具有 PfMSP-1（19）特异性 MBC 的受体小鼠中，在受到转基因伯氏疟原虫的攻击后，并未实现保护。我们的发现表明，短暂的浆细胞结合 PfMSP-1（19）诱导的 MBC 维持回忆性 IgG 反应的能力差，导致 PfMSP-1（19）特异性 IgG 产生无法有助于抗感染。
