Laboratory of Aquatic Animal Diseases, Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam, 52828, Republic of Korea.
Earwynbio Co., Ltd., 206 Sungjangjiwon-dong, 991 Worasan-ro, Munsan, Jinju, Gyeongnam, 52839, Republic of Korea.
Fish Shellfish Immunol. 2024 Jul;150:109565. doi: 10.1016/j.fsi.2024.109565. Epub 2024 Apr 17.
The jawless vertebrates (agnathans/cyclostomes) are ancestral animals comprising lampreys and hagfishes as the only extant representatives. They possess an alternative adaptive immune system (AIS) that uses leucine-rich repeats (LRR)-based variable lymphocyte receptors (VLRs) instead of the immunoglobulin (Ig)-based antigen receptors of jawed vertebrates (gnathostomes). The different VLR types are expressed on agnathan lymphocytes and functionally resemble gnathostome antigen receptors. In particular, VLRB is functionally similar to the B cell receptor and is expressed and secreted by B-like lymphocytes as VLRB antibodies that bind antigens with high affinity and specificity. The potential repertoire scale of VLR-based antigen receptors is believed to be at least comparable to that of Ig-based systems. VLR proteins inherently possess characteristics that render them excellent candidates for biotechnological development, including tractability to recombinant approaches. In recent years, scientists have explored the biotechnological development and utility of VLRB proteins as alternatives to conventional mammalian antibodies. The VLRB antibody platform represents a non-traditional approach to generating a highly diverse repertoire of unique antibodies. In this review, we first describe some aspects of the biology of the AIS of the jawless vertebrates, which recognizes antigens by means of unique receptors. We then summarize reports on the development of VLRB-based antibodies and their applications, particularly those from the inshore hagfish (Eptatretus burgeri) and their potential uses to address microbial diseases in aquaculture. Hagfish VLRB antibodies (we call Ccombodies) are being developed and improved, while obstacles to the advancement of the VLRB platform are being addressed to utilize VLRBs effectively as tools in immunology. VLRB antibodies for novel antigen targets are expected to emerge to provide new opportunities to tackle various scientific questions. We anticipate a greater interest in the agnathan AIS in general and particularly in the hagfish AIS for greater elucidation of the evolution of adaptive immunity and its applications to address microbial pathogens in farmed aquatic animals and beyond.
无颌脊椎动物（无颌类/圆口类）是由七鳃鳗和盲鳗组成的原始动物，是现存的唯一代表。它们拥有一种替代适应性免疫系统（AIS），该系统使用富含亮氨酸的重复序列（LRR）为基础的可变淋巴细胞受体（VLR），而不是有颌脊椎动物（颌口类）的免疫球蛋白（Ig）为基础的抗原受体。不同的 VLR 类型在无颌类淋巴细胞上表达，在功能上类似于颌口类的抗原受体。特别是，VLRB 在功能上类似于 B 细胞受体，并由 B 样淋巴细胞表达和分泌为 VLRB 抗体，该抗体以高亲和力和特异性结合抗原。基于 VLR 的抗原受体的潜在库规模据信至少与基于 Ig 的系统相当。VLR 蛋白本身具有使其成为生物技术开发的优秀候选物的特性，包括对重组方法的可操作性。近年来，科学家们已经探索了 VLRB 蛋白作为替代传统哺乳动物抗体的生物技术开发和应用。VLRB 抗体平台代表了一种非传统的方法，可以产生高度多样化的独特抗体库。在这篇综述中，我们首先描述了无颌脊椎动物 AIS 的生物学的一些方面，该系统通过独特的受体识别抗原。然后，我们总结了关于基于 VLRB 的抗体的开发和应用的报告，特别是来自近海盲鳗（Eptatretus burgeri）的报告，及其在水产养殖中应对微生物疾病的潜在用途。盲鳗 VLRB 抗体（我们称之为 Ccombodies）正在被开发和改进，而克服 VLRB 平台的障碍以有效地将 VLRB 用作免疫学工具的问题也在得到解决。用于新型抗原靶标的 VLRB 抗体预计将出现，为解决各种科学问题提供新的机会。我们预计人们对无颌类 AIS 的兴趣会增加，特别是对盲鳗 AIS 的兴趣会增加，以便更深入地了解适应性免疫的进化及其在解决养殖水生动物和其他动物中的微生物病原体方面的应用。
