|Tanyi Zhang, Xueqian Cheng, Di Yu, Fuyu Lin, Ning Hou, Yanbin Fu, Yonghe Ma, Liming Ren, Xiao Yang and Yaofend Zhao. Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice. Frontiers in Immunology. DOI: 10.3389/immu2018.|
Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice
Tanyi Zhang, Xueqian Cheng, Di Yu, Fuyu Lin, Ning Hou, Xuan Cheng, Shanshan Hao, Jingjing Wei, Li Ma, Yanbin Fu, Yonghe Ma, Liming Ren, aitang Han, Shuyang Yu, Xiao Yang and Yaofend Zhao
Frontiers in Immunology
Nano-antibodies possess great potential in many applications. However, they are naturally derived from heavy chain-only antibodies (HcAbs), which lack light chains and the CH1 domain, and are only found in camelids and sharks. In this study, we investigated whether the precise genetic removal of the CHI exon of the y1 gene enabled the production of a functional heavy chain-only lgG1 in mice. IgG1 heavy chain dimers lacking associated light chains were detected in the sera of the genetically modified mice. However, the genetic modification led to decreased expression of laG1 but increased expression of other lgG subclasses. The genetically modified mice showed a weaker immune response to specific antigens compared with wild type mice. Using a phage display approach, antigen-specific, single domain VH antibodies could be screened from the mice but exhibited much weaker antigen binding affinity than the conventional monoclonal antibodies. Although the strategy was only partially successful, this study confirms the feasibility of producing desirable nano-bodies with appropriate genetic modifications in mice.