Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany.
Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673, Singapore.
Sci Adv. 2021 Jan 1;7(1). doi: 10.1126/sciadv.abd8180. Print 2021 Jan.
The rules underlying the structure of antigen receptor repertoires are not yet fully defined, despite their enormous importance for the understanding of adaptive immunity. With current technology, the large antigen receptor repertoires of mice and humans cannot be comprehensively studied. To circumvent the problems associated with incomplete sampling, we have studied the immunogenetic features of one of the smallest known vertebrates, the cyprinid fish sp. "Singkep" ("minifish"). Despite its small size, minifish has the key genetic facilities characterizing the principal vertebrate lymphocyte lineages. As described for mammals, the frequency distributions of immunoglobulin and T cell receptor clonotypes exhibit the features of fractal systems, demonstrating that self-similarity is a fundamental property of antigen receptor repertoires of vertebrates, irrespective of body size. Hence, minifish achieve immunocompetence via a few thousand lymphocytes organized in robust scale-free networks, thereby ensuring immune reactivity even when cells are lost or clone sizes fluctuate during immune responses.
尽管抗原受体库的结构所遵循的规则对于理解适应性免疫具有极其重要的意义,但这些规则尚未得到完全定义。受当前技术的限制,无法全面研究小鼠和人类如此庞大的抗原受体库。为了规避与不完全采样相关的问题,我们研究了一种已知的最小脊椎动物——鲤科小鱼“Singkep”(“minifish”)的免疫遗传学特征。尽管体型很小,minifish 却拥有构成主要脊椎动物淋巴细胞谱系的关键遗传设施。与哺乳动物一样,免疫球蛋白和 T 细胞受体克隆型的频率分布呈现出分形系统的特征,这表明自相似性是脊椎动物抗原受体库的基本特性,而与体型无关。因此,minifish 通过几千个组织成强大无标度网络的淋巴细胞来实现免疫能力,从而确保了即使在免疫反应期间细胞丢失或克隆大小波动时也具有免疫反应性。