Long-term maternal imprinting of the specific B cell repertoire by maternal antibodies.
Maternal antibodies protect newborns whilst they are immunologically immature. This study shows that maternal antibodies can also shape the B cell repertoire of the offspring long after the maternal antibodies themselves become undetectable. V(H)DJ(H) gene-targeted (VI10) mice expressing a heavy chain specific for vesicular stomatitis virus (VSV) produce a 20-fold increased spontaneous titer of VSV-neutralizing antibodies. When transferred from mother to offspring, these antibodies prevented accumulation of Ag-specific transitional type 2 and marginal zone B cells with an activated phenotype and favored selection to the B cell follicles. This effect was B cell-intrinsic and lasted up to adulthood. The pups nursed by mothers producing specific antibodies developed higher endogenous antibody titers of this specificity which perpetuated the effects of specific B cell selection into the mature follicular compartment, presumably by blocking auto-Ag-dependent development of transitional type 2 B cells in the spleen. This repertoire change was functional, as following infection of adult mice with VSV, those pups that had received specific maternal antibodies as neonates had increased pre-immune titers and mounted strong early IgG neutralizing antibodies.
Fink
Katja
K
Institute of Experimental Immunology, University Hospital Zurich, Zurich, Switzerland. katja.fink@alumni.ethz.ch
Zellweger
Raphael
R
Weber
Jacqueline
J
Manjarrez-Orduno
Nataly
N
Holdener
Martin
M
Senn
Beatrice M
BM
Hengartner
Hans
H
Zinkernagel
Rolf M
RM
Macpherson
Andrew J
AJ
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D018392:Genomic Imprinting / Q000276:immunology*; D007107:Immune System / Q000254:growth & development*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D051379:Mice; D018353:Rhabdoviridae Infections / Q000276:immunology; D013995:Time; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000906:Antibodies; D000914:Antibodies, Viral