Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers

Abstract

Summary: Maternal antibodies (MatAbs) protect offspring from infections but limit their responses to vaccination. The mechanisms of this inhibition are still debated. Using murine early-life immunization models mimicking the condition prevailing in humans, we observed the induction of CD4-T, T follicular helper, and germinal center (GC) B cell responses even when early-life antibody responses were abrogated by MatAbs. GC B cells induced in the presence of MatAbs form GC structures and exhibit canonical GC changes in gene expression but fail to differentiate into plasma cells and/or memory B cells in a MatAb titer-dependent manner. Furthermore, GC B cells elicited in the presence or absence of MatAbs use different VH and Vk genes and show differences in genes associated with B cell differentiation and isotype switching. Thus, MatAbs do not prevent B cell activation but control the output of the GC reaction both quantitatively and qualitatively, shaping the antigen-specific B cell repertoire. : Maternal antibodies (MatAbs) protect offspring from infections but limit their vaccine responses through still poorly known mechanisms. Vono et al. report that MatAbs do not prevent B cell activation or germinal center formation but control plasma cell and memory B cell differentiation, shaping the long-term antigen-specific B cell repertoire. Keywords: immunization, maternal antibodies, neonates, repertoire, germinal centers, epitope masking