B细胞激活概要1.pptVIP

TI-1 antigens are polyclonal B cell activators at high concentrations, whereas at low concentrations they induced an antigen-specific antibody response B cell activation by TI-2 Ag is greatly enhanced by cytokines, which can also induce isotype switching Gal ? (1-3) gal ? (1-4) glcNAc - R gal-? gal-? (1-4) glcNAc R 半乳糖 乙酰乳糖胺 糖脂 （?半乳糖-乙酰氨基葡萄糖） 猪-人异种移植 超急排斥抗原 半乳糖转移酶基因的进化和非协调性异种器官移植中的超急性排斥 超急排斥 猪?人非协调性异种器官移植 超急排斥抗原 半乳糖转移酶基因 + + + + ? ? ? 异种天然抗体 (XNA) 低等 高等 哺乳 新世 旧世 类 动物 动物 动物 界猴 界猴 人猿 人类 GT 半乳糖基转移酶 (GT, galactosyl transferase) 超急排斥抗原HAR 猪血管内皮细胞 人血流 Affinity between Ag-Ab reaction and equilibrium constant K Affinity maturation good fit poor fit applying the Law of Mass Action 蛋白质抗原多次免 疫后抗体含量和抗体亲 和力明显上升，这一上 升主要针对 IgG 而非 IgM抗体 Affinity maturation 亲和力成熟主要发生在 二次免疫应答 Antibody level Antibody affinity Day 1 Day 21 Day 7 Day 14 Secondary immunization immunization DNA DNA DNA DNA DNA DNA DNA DNA DNA DNA 脾 脾细胞 建系 DNA 扩增 DNA 测序 分析抗体重链和轻链基因核苷酸序列变异性的实验步骤 1/1000bp vs 1/107?1010 Day 1 Day 21 Day 7 Day 14 Secondary immunization immunization B1 Ag T细胞高频突变 B2 B3 B1 Ag Ag Ag 选择 B2 Ag Ig亲和力成熟 中低亲和力 高亲和力 Somatic hypermutation in centroblasts Affinity maturation Isotype switching dark zone light zone light zone low affinity apoptosis high affinity FDC: follicular dendritic cell Centrocyte Centroblast (activated B cell) B cells Selection of high affinity centrocytes by binding to Ag-Ab complexes on FDCs low affinity Plasmablast Plasma cell Memory cell Macrophage Maturation to memory or plasma cells Ab Germinal Center After T-cell dependent activation, B cells undergo rounds of mutation and selection for higher affinity, ultimately resulting in high-affinity memory B cells and antibody secreted from