Zhang Yang, Garcia-Ibanez Laura, Toellner Kai-Michael
Institute for Immunology and Immunotherapy, University of Birmingham Medical School, Birmingham, UK.
Immunol Rev. 2016 Mar;270(1):8-19. doi: 10.1111/imr.12396.
Germinal centers (GC) are the main sites where antigen-activated B-cell clones expand and undergo immunoglobulin gene hypermutation and selection. Iterations of this process will lead to affinity maturation, replicating Darwinian evolution on the cellular level. GC B-cell selection can lead to four different outcomes: further expansion and evolution, apoptosis (non-selection), or output from the GC with differentiation into memory B cells or plasma cells. T-helper cells in GC have been shown to have a central role in regulating B-cell selection by sensing the density of major histocompatibility complex (MHC):peptide antigen complexes. Antigen is provided on follicular dendritic cells in the form of immune complex. Antibody on these immune complexes regulates antigen accessibility by shielding antigen from B-cell receptor access. Replacement of antibody on immune complexes by antibody generated from GC-derived plasma cell output will gradually reduce the availability of antigen. This antibody feedback can lead to a situation where a slow rise in selection stringency caused by a changing environment leads to directional evolution toward higher affinity antibody.
生发中心（GC）是抗原激活的B细胞克隆扩增并经历免疫球蛋白基因超突变和选择的主要场所。这一过程的反复进行将导致亲和力成熟，在细胞水平上复制达尔文进化。GC B细胞的选择可导致四种不同结果：进一步扩增和进化、凋亡（未被选择），或从生发中心输出并分化为记忆B细胞或浆细胞。已证明生发中心的辅助性T细胞通过感知主要组织相容性复合体（MHC）：肽抗原复合物的密度，在调节B细胞选择中起核心作用。抗原以免疫复合物的形式存在于滤泡树突状细胞上。这些免疫复合物上的抗体通过屏蔽抗原使其不被B细胞受体识别来调节抗原的可及性。由生发中心衍生的浆细胞输出产生的抗体取代免疫复合物上的抗体，将逐渐降低抗原的可用性。这种抗体反馈可能导致一种情况，即不断变化的环境导致选择严格性缓慢上升，从而导致向更高亲和力抗体的定向进化。
