Annual Review of Animal Biosciences The Immunoglobulins: New Insights, Implications, and Applications Yi Sun, 1 Tian Huang, 2 Lennart Hammarström, 3 and Yaofeng Zhao 4 1 Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, Shandong, People’s Republic of China; email: sunyi@cau.edu.cn 2 Henan Engineering Laboratory for Mammary Bioreactor, School of Life Sciences, Henan University, Kaifeng 475004, Henan, People’s Republic of China; email: huangtian@henu.edu.cn 3 Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska Hospital Huddinge, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden; email: lennart.hammarstrom@ki.se 4 State Key Laboratory of Agrobiotechnology, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing 100193, People’s Republic of China; email: yaofengzhao@cau.edu.cn Annu. Rev. Anim. Biosci. 2020. 8:145–69 First published as a Review in Advance on December 17, 2019 The Annual Review of Animal Biosciences is online at animal.annualreviews.org https://doi.org/10.1146/annurev-animal-021419- 083720 Copyright © 2020 by Annual Reviews. All rights reserved Keywords immunoglobulin heavy chain, IgM, IgD, IgY(Fc), heavy chain–only antibody, ultralong CDR3 H3 Abstract Immunoglobulins (Igs), as one of the hallmarks of adaptive immunity, first arose approximately 500 million years ago with the emergence of jawed ver- tebrates.Two events stand out in the evolutionary history of Igs from car- tilaginous fish to mammals: (a) the diversification of Ig heavy chain (IgH) genes, resulting in Ig isotypes or subclasses associated with novel functions, and (b) the diversification of genetic and structural strategies, leading to the creation of the antibody repertoire we know today. This review first gives an overview of the IgH isotypes identified in jawed vertebrates to date and then highlights the implications or applications of five new recent discover- ies arising from comparative studies of Igs derived from different vertebrate species. 145 Annu. Rev. Anim. Biosci. 2020.8:145-169. Downloaded from www.annualreviews.org Access provided by 207.241.225.246 on 05/07/20. For personal use only.