title: Molecular studies on the diversification of hemagglutinin-specific human neonatal repertoire subsequent to immunization with naked DNA.
abstract: It is well known that newborns and infants respond poorly to immunization with influenza virus vaccines. The poor response of neonates may be related to restricted B cell repertoire and high susceptibility of neonates to high dose tolerance. Protective antibody response against hemagglutinin (HA) of influenza virus is a T-dependent response. While the immunization of neonates with live virus caused a long lasting unresponsiveness, the immunization with a plasmid containing influenza virus HA circumvents the neonatal unresponsiveness. Genetic immunization primes efficiently neonatal HA-specific B cells, and induces memory cell enabling the animals to develop a strong secondary response and to survive to challenge with a lethal dose. The most striking effect of neonatal immunization consists of a shift of neonatal HA-specific B cell repertoire to adult-type as assessed by analysis of reactivity pattern of HA-specific clonotypes. The diversification is associated with the induction of germinal centers, increased number of B220(+)GL-7(+) cells and with the re-expression of RAG genes. This suggests that the receptor revision may contribute to the diversification of HA-specific neonatal B repertoire.
authors.affiliation: Department of Microbiology, Box 11124, Mt. Sinai School of Medicine, One Gustave L Levy Place, Building 16-60, New York, NY 10029, USA. bona@mssm.edu
authors.forename: Constantin
authors.initials: C
authors.lastname: Bona
authors.forename: Dorel
authors.initials: D
authors.lastname: Radu
authors.forename: Takao
authors.initials: T
authors.lastname: Kodera
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D004279:DNA, Viral / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007231:Infant, Newborn; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D004279:DNA, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA