Antibodies are key players of adaptive immunity to pathogens, bridging antigen recognition with innate immunity. The humoral adaptive immunity utilizes genetic mechanisms to generate an enormous diversity of antibody variable (V) regions which are responsible for antigen-binding specificities. The genetic processes of V, D (diversity), and J (joining) recombination and somatic hypermutation occur during B cell development in the bone marrow and upon encounters of antigen in the periphery. The diversity of antibody repertoires is primarily created by these conventional mechanisms through the introduction of combinatorial and junctional diversity in the V regions, as well as point mutations in the rearranged V regions after contact of naïve or memory B cells with antigens.
Recent technological advancements in human B cell repertoire sequencing and monoclonal antibody analytics have revealed that the immune systems can employ additional mechanisms and strategies to increase antibody diversification. These ‘unconventional’ routes and strategies modulate the antigen-binding sites of antibodies via post-translational modifications, insertions of long or short amino acid sequences, use of non-protein cofactors, and conformational dynamics. Although more and more such cases are being identified, the broader molecular basis, the biological roles, and the therapeutic applications of each mechanism remain obscure. A call for the wider antibody research community to work together is needed to deepen the understanding in this new field. Reports with new examples and mechanistic details should shed light on this alternative layer of diversification for the adaptability and plasticity of the immune systems.
This Research Topic aims to highlight articles that explore the unorthodox mechanisms and strategies in antibody-antigen binding diversity. We welcome submissions on antibody diversification of immune repertoires with Original Research and Review articles focusing on, but not limited to, the following specific sub-topics:
1) Antibody diversification through post-translational modifications, such as N- or O-linked glycans, tyrosine sulfation, disulfide-bond formation
2) Antibody diversification through non-protein cofactors such as metal ions and heme
3) Antibody diversification through non-immunoglobin V-region insertions
4) Antibody diversification through conformational dynamics such as conformational isomerism and reconfiguration of the antigen-binding regions
5) Any other nonconventional antibody diversification strategies
6) Biological or therapeutic implications of antibody diversification
7) Unconventional aspects on genetic processes of VDJ recombination and somatic hypermutation
8) Production and characterization of antibodies with nonconventional diversity
Dr. Xiaotian Zhong is an employee at Pfizer Inc, involved in the development of antibody and protein therapeutics. The other Topic Editors declare no competing interests in relation to the topic theme.
Antibodies are key players of adaptive immunity to pathogens, bridging antigen recognition with innate immunity. The humoral adaptive immunity utilizes genetic mechanisms to generate an enormous diversity of antibody variable (V) regions which are responsible for antigen-binding specificities. The genetic processes of V, D (diversity), and J (joining) recombination and somatic hypermutation occur during B cell development in the bone marrow and upon encounters of antigen in the periphery. The diversity of antibody repertoires is primarily created by these conventional mechanisms through the introduction of combinatorial and junctional diversity in the V regions, as well as point mutations in the rearranged V regions after contact of naïve or memory B cells with antigens.
Recent technological advancements in human B cell repertoire sequencing and monoclonal antibody analytics have revealed that the immune systems can employ additional mechanisms and strategies to increase antibody diversification. These ‘unconventional’ routes and strategies modulate the antigen-binding sites of antibodies via post-translational modifications, insertions of long or short amino acid sequences, use of non-protein cofactors, and conformational dynamics. Although more and more such cases are being identified, the broader molecular basis, the biological roles, and the therapeutic applications of each mechanism remain obscure. A call for the wider antibody research community to work together is needed to deepen the understanding in this new field. Reports with new examples and mechanistic details should shed light on this alternative layer of diversification for the adaptability and plasticity of the immune systems.
This Research Topic aims to highlight articles that explore the unorthodox mechanisms and strategies in antibody-antigen binding diversity. We welcome submissions on antibody diversification of immune repertoires with Original Research and Review articles focusing on, but not limited to, the following specific sub-topics:
1) Antibody diversification through post-translational modifications, such as N- or O-linked glycans, tyrosine sulfation, disulfide-bond formation
2) Antibody diversification through non-protein cofactors such as metal ions and heme
3) Antibody diversification through non-immunoglobin V-region insertions
4) Antibody diversification through conformational dynamics such as conformational isomerism and reconfiguration of the antigen-binding regions
5) Any other nonconventional antibody diversification strategies
6) Biological or therapeutic implications of antibody diversification
7) Unconventional aspects on genetic processes of VDJ recombination and somatic hypermutation
8) Production and characterization of antibodies with nonconventional diversity
Dr. Xiaotian Zhong is an employee at Pfizer Inc, involved in the development of antibody and protein therapeutics. The other Topic Editors declare no competing interests in relation to the topic theme.