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

TY - JOUR

T1 - Maternal Antibodies Inhibit Neonatal and Infant Responses to Vaccination by Shaping the Early-Life B Cell Repertoire within Germinal Centers

AU - Vono, Maria

AU - Eberhardt, Christiane Sigrid

AU - Auderset, Floriane

AU - Mastelic-Gavillet, Beatris

AU - Lemeille, Sylvain

AU - Christensen, Dennis

AU - Andersen, Peter

AU - Lambert, Paul Henri

AU - Siegrist, Claire Anne

PY - 2019/8/13

Y1 - 2019/8/13

N2 - 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.

AB - 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.

KW - epitope masking

KW - germinal centers

KW - immunization

KW - maternal antibodies

KW - neonates

KW - repertoire

U2 - 10.1016/j.celrep.2019.07.047

DO - 10.1016/j.celrep.2019.07.047

M3 - Journal article

C2 - 31412246

AN - SCOPUS:85070185277

SN - 2639-1856

VL - 28

SP - 1773-1784.e5

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -