Deciphering the antibody-microbiota axis in early life

ongoing

Immunoglobulins (Igs) are thought to influence formation of the microbiota composition during a critical window of opportunity in early life. Yet, the antigen binding profiles of these Igs are vastly unknown, and it is incompletely understood how early misguided immune education contributes to the development of allergies or asthma. On an even more fundamental level, it is also unclear if or how B cell receptor (BCR) sequences of different individuals converge to binding similar microbiota antigens and how such responses form in early life. Here, we will leverage phage display as well as novel approaches to study BCR sequence/Ig function relationships, focusing on the following objectives & research questions: a) How do immune exposures in early life shape Ig repertoires and influence health later on? We hypothesize that Ig repertoire development depends on the birth mode, duration of breast feeding, & antibiotics treatments. Here, we will deeply profile the Ig repertoires of mother-child dyads against 600,000 rationally selected microbiota antigens. We will also study the immune repertoires of children with allergies and mine these data sets for associations with early life Ig data sets. b) Do BCR sequences of different individuals converge to binding similar antigens? As observed for some viral antigens, we hypothesize that also universal responses towards bacterial antigens exist and we can capture such sequences in early life. We will apply state of the art and novel proprietary methodologies to link BCR sequences with Ig binding in adults & infants. Linking BCR sequence information with the actual antigen targets, will contribute to understanding the sequence-function relationship of Ig binding and their formation in early life. Deep profiling of mother-child dyads will provide new insights to the development of Ig repertoires. By comparing these datasets with allergic children may also reveal links between early immune education & lasting impacts on health.