title: Unresponsiveness to lymphoid-mediated signals at the neonatal follicular dendritic cell precursor level contributes to delayed germinal center induction and limitations of neonatal antibody responses to T-dependent antigens.
abstract: The factors limiting neonatal and infant IgG Ab responses to T-dependent Ags are only partly known. In this study, we assess how these B cell responses are influenced by the postnatal development of the spleen and lymph node microarchitecture. When BALB/c mice were immunized with alum-adsorbed tetanus toxoid at various stages of their immune development, a major functional maturation step for induction of serum IgG, Ab-secreting cells, and germinal center (GC) responses was identified between the second and the third week of life. This correlated with the development of the follicular dendritic cell (FDC) network, as mature FDC clusters only appeared at 2 wk of age. Adoptive transfer of neonatal splenocytes into adult SCID mice rapidly induced B cell follicles and FDC precursor differentiation into mature FDC, indicating effective recruitment and signaling capacity of neonatal B cells. In contrast, adoptive transfer of adult splenocytes into neonatal SCID mice induced primary B cell follicles without any differentiation of mature FDC and failed to correct limitations of tetanus toxoid-induced GC. Thus, unresponsiveness to lymphoid-mediated signals at the level of neonatal FDC precursors delays FDC maturation and GC induction, thus limiting primary Ab-secreting cell responses to T-dependent Ags in early postnatal life.
authors.affiliation: Department of Pathology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, Geneva, Switzerland. Maria.Pihlgren@medecine.unige.ch
authors.forename: Maria
authors.initials: M
authors.lastname: Pihlgren
authors.forename: Chantal
authors.initials: C
authors.lastname: Tougne
authors.forename: Paola
authors.initials: P
authors.lastname: Bozzotti
authors.forename: Alma
authors.initials: A
authors.lastname: Fulurija
authors.forename: Michel A
authors.initials: MA
authors.lastname: Duchosal
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000166:cytology / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054382:Chemokine CXCL13; D019743:Chemokines, CXC / Q000502:physiology; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010047:Ovalbumin / Q000276:immunology; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D006241:Haptens; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D013745:Tetanus Toxoid; D014301:Trinitrobenzenes; C038600:trinitrophenyl-ovalbumin; D010047:Ovalbumin