Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers.
Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers.
复制标题
亲和力成熟受到生发中心自然杀伤细胞抑制的损害。
DOI：
10.1016/j.celrep.2018.08.075
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发表时间：
2018-09-25
期刊：
影响因子：
8.8
通讯作者：
Waggoner SN
中科院分区：
文献类型：
--
作者：
Rydyznski CE;Cranert SA;Zhou JQ;Xu H;Kleinstein SH;Singh H;Waggoner SN
自然杀伤（NK）细胞限制免疫诱导的滤泡辅助性T细胞和生发中心B细胞反应。Rydyznski等人将NK细胞穿孔依赖功能与抗原特异性B细胞体内体细胞超突变的频率和质量降低联系起来。针对NK细胞活性的策略可以增强疫苗诱导的高亲和力保护性抗体的产生。必须优化生发中心（GC）反应中免疫球蛋白序列的体细胞超突变，以在接种疫苗后引发高亲和力的保护性抗体。我们将自然杀伤（NK）细胞暴露为抗原反应性B细胞体细胞超突变的稳健负调节因子。在使用铝佐剂半抗原蛋白结合疫苗后，NK细胞限制滤泡辅助性T细胞（TFH）和GC B细胞的频率和抗原特异性免疫球蛋白的滴度。这种抑制是穿孔素依赖的，表明NK细胞杀死一个或多个对GC发育至关重要的细胞。在表现能力NK细胞存在的情况下，抗原特异性GC B细胞获得较少的突变，包括较少的非同义替换和与抗体亲和力增加相关的突变。因此，NK细胞限制了GC反应的强度，从而抑制了高亲和力抗体的疫苗激发。在疫苗接种期间规避NK细胞的这种活性具有增强体液免疫和促进疫苗引起的疾病预防的强大潜力。
Natural killer (NK) cells limit immunization-elicited follicular helper T cell and germinal center B cell responses. Rydyznski et al. link perforin-dependent functions of NK cells to a reduced frequency and quality of somatic hypermutation within antigen-specific B cells. Strategies targeting this NK cell activity may enhance vaccination-induced generation of high-affinity protective antibodies. Somatic hypermutation of immunoglobulin sequences in germinal center (GC) reactions must be optimized to elicit high-affinity, protective antibodies after vaccination. We expose natural killer (NK) cells as robust negative regulators of somatic hypermutation in antigen-reactive B cells. NK cells restrict follicular helper T cell (TFH) and GC B cell frequencies and titers of antigen-specific immunoglobulin after administration of alum-adjuvanted hapten-protein conjugate vaccines. This inhibition is perforin dependent, suggesting that NK cells kill one or more cells critical for GC development. In the presence of perforin-competent NK cells, antigen-specific GC B cells acquire fewer mutations, including less frequent generation of non-synonymous substitu-tions and mutations associated with increased antibody affinity. Thus, NK cells limit the magnitude of GC reactions and thereby restrain vaccine elicitation of high-affinity antibodies. Circumventing this activity of NK cells during vaccination has strong potential to enhance humoral immunity and facilitate vaccine-elicited prevention of disease.
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影响因子：
15.3
作者：
McHeyzer-Williams, M G;McLean, M J;Lalor, P A;Nossal, G J
通讯作者：
Nossal, G J
影响因子：
8.7
作者：
MAKELA, O;KARJALAINEN, K
通讯作者：
KARJALAINEN, K
影响因子：
6.4
作者：
Pollock, KGJ;Conacher, M;Brewer, JM
通讯作者：
Brewer, JM
影响因子：
4.4
作者：
Rabinovich, BA;Li, J;Miller, RG
通讯作者：
Miller, RG
影响因子：
64.8
作者：
KAGI, D;LEDERMANN, B;HENGARTNER, H
通讯作者：
HENGARTNER, H