Public antibodies: convergent signatures in human humoral immunity against pathogens

Abstract

ABSTRACT The human humoral immune system has evolved to recognize a vast array of pathogenic threats. This ability is primarily driven by the immense diversity of antibodies generated by gene rearrangement during B cell development. However, different people often produce strikingly similar antibodies when exposed to the same antigen—known as public antibodies. Public antibodies not only reflect the immune system’s ability to consistently select for optimal B cells but can also serve as signatures of the humoral responses triggered by infection and vaccination. In this Minireview, we examine and compare public antibody identification methods, including the identification criteria used based on V(D)J gene usage and similarity in the complementarity-determining region three sequences, and explore the molecular features of public antibodies elicited against common pathogens, including viruses, protozoa, and bacteria. Finally, we discuss the evolutionary significance and potential applications of public antibodies in informing the design of germline-targeting vaccines, predicting escape mutations in emerging viruses, and providing insights into the process of affinity maturation. The ongoing discovery of public antibodies in response to emerging pathogens holds the potential to improve pandemic preparedness, accelerate vaccine design efforts, and deepen our understanding of human B cell biology.