The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations.
The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations.
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DOI：
10.1016/j.vaccine.2016.04.023
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发表时间：
2016-05-27
期刊：
影响因子：
5.5
通讯作者：
Blomberg BB
中科院分区：
文献类型：
--
作者：
Frasca D;Diaz A;Romero M;Blomberg BB
疫苗能否成功诱导保护性抗体应答取决于长寿浆细胞（PC）和记忆B细胞的寿命。我们以前已经表明，体内抗体反应的一种新的流感疫苗，离体浆母细胞反应，体外B细胞功能，测定AID（激活诱导的胞苷脱氨酶），和转录因子E47，显着相关，并在老年人减少。我们假设，由于老年人的AID减少，产生记忆B细胞的能力也会降低，但我们的研究结果表明，记忆B细胞在老年人中得以维持，这可能是由于对重复接种疫苗的反应进一步扩增。我们招募了至少连续两个流感疫苗接种季节接种的年轻人和老年人，其中疫苗中的甲型流感病毒株H1N1和H3 N2与前一年相同。用CpG/IL 2培养PBMC以测量IgG疫苗特异性记忆B细胞的频率。通过血凝抑制试验测量血清抗体反应。流式细胞术检测血浆母细胞。令人惊讶的是，流感疫苗特异性记忆B细胞和浆母细胞的频率在年轻人和老年人中相似，但接种后血清滴度的倍数增加在老年人中较低，尽管大多数老年人是血清保护的。然后，我们测量了转录因子Blimp-1（被认为是PC分化的主要调节因子），发现它在老年人与年轻人的B细胞培养物中显著降低，以及E47/AID和IgG分泌。综上所述，这些结果表明老年人记忆B细胞向PC分化受损。
The success of a vaccine in inducing a protective antibody response depends on the longevity of both long-lived plasma cells (PC) and memory B cells. We have previously shown that the in vivo antibody response to a new influenza vaccine, the ex vivo plasmablast response, the in vitro B cell function, measured by AID (activation-induced cytidine deaminase), and the transcription factor E47, are significantly associated and decreased in elderly individuals. We hypothesized that because AID is decreased in the elderly, the ability to generate memory B cells would also be decreased, but our findings here show that memory B cells are maintained in the elderly probably due to further amplification in response to repeated vaccination. We recruited young and elderly individuals immunized in at least two consecutive influenza vaccine seasons in which the influenza A viral strains H1N1 and H3N2 in the vaccine were the same as in the previous year. PBMC were cultured with CpG/IL2 to measure the frequency of IgG vaccine-specific memory B cells. Serum antibody response was measured by hemagglutination inhibition assay. Blood plasmablasts were measured by flow cytometry. Surprisingly, the frequencies of influenza vaccine-specific memory B cells and plasmablasts were similar in young and elderly individuals, but the fold-increase in serum titers after vaccination was lower in the elderly although most of the elderly were seroprotected. We then measured the transcription factor Blimp-1, considered the master regulator of PC differentiation, and found it significantly reduced in cultures of B cells from elderly versus young individuals, as well as E47/AID and IgG secretion. Taken together, these results suggest an impaired memory B cell to PC differentiation in the elderly.