The immunoglobulin constant region contributes to affinity and specificity

A central dogma in immunology is that antibody specificity is solely the result of variable (V)-region interactions with an antigen. However, this view is not tenable in light of numerous reports that constant heavy (CH) domains can affect binding affinity and specificity and V-region structure. Kinetic and thermodynamic proof for the occurrence of this phenomenon is now available. CH-region effects on affinity and specificity suggest new mechanisms for generating antibody diversity and polyreactivity (multispecificity) that impact current views on idiotype regulation, autoimmunity, and B cell selection and change our understanding of vaccine responses.