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

• Published in: Cell reports (Cambridge) 2019-08, Vol.28 (7), p.1773-1784.e5
• Main Authors: Vono, Maria, Eberhardt, Christiane Sigrid, Auderset, Floriane, Mastelic-Gavillet, Beatris, Lemeille, Sylvain, Christensen, Dennis, Andersen, Peter, Lambert, Paul-Henri, Siegrist, Claire-Anne
• Format: Article
• Language: English
• Subjects: epitope masking; germinal centers; immunization; maternal antibodies; neonates; repertoire
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.07.047

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. [Display omitted] •MatAbs inhibit early-life antibody responses but do not prevent B cell activation•Germinal center formation occurs despite MatAbs, but their output is altered•Plasma cell and memory B cell differentiation is affected in a titer-dependent manner•GC B cells elicited in the presence or absence of MatAbs express distinct BCRs 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.