Chen Z, Koralov S B, Gendelman M, Carroll M C, Kelsoe G
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2000 May 1;164(9):4522-32. doi: 10.4049/jimmunol.164.9.4522.
Deficiency in CD21/CD35 by disruption of the Cr2 loci leads to impaired humoral immune responses. In this study, we detail the role of CD21/CD35 on Ab responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken gamma-globulin. Surprisingly, Cr2-/- mice generate significant Ab responses and germinal center (GC) reactions to low doses of this Ag in alum, although the magnitude of their responses is much reduced in comparison with those of Cr2+/- and C57BL/6 controls. Increasing Ag dose partially corrected this deficit. In situ study of the somatic genetics of GC B cells demonstrated that VDJ hypermutation does not require CD21/CD35, and Cr2-/- mice exhibited enhanced affinity maturation of serum Ab in the post-GC phase of the primary response. On the other hand, Cr2-/- mice displayed accelerated loss of serum Ab and long-lived Ab-forming cells. These observations suggest that B cell activation/survival signals mediated by CD21 and/or the retention of Ag by CD21/CD35 play important roles in the generation, quality, and maintenance of serum Ab.
通过破坏Cr2基因座导致CD21/CD35缺乏会致使体液免疫反应受损。在本研究中，我们详细阐述了CD21/CD35在对半抗原（4-羟基-3-硝基苯基）乙酰与鸡γ球蛋白偶联物的抗体反应中的作用。令人惊讶的是，Cr2基因敲除小鼠对明矾中低剂量的这种抗原产生了显著的抗体反应和生发中心（GC）反应，尽管与Cr2+/-和C57BL/6对照相比，它们的反应强度大大降低。增加抗原剂量部分纠正了这一缺陷。对GC B细胞体细胞遗传学的原位研究表明，VDJ超突变不需要CD21/CD35，并且Cr2基因敲除小鼠在初次反应的GC后阶段血清抗体表现出增强的亲和力成熟。另一方面，Cr2基因敲除小鼠显示出血清抗体和长寿抗体形成细胞的加速丧失。这些观察结果表明，由CD21介导的B细胞活化/存活信号和/或CD21/CD35对抗原的保留在血清抗体的产生、质量和维持中起重要作用。
