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.
Early life antibody responses are characterized by a rapid decline, such that antigen‐specific IgG antibodies decline to baseline levels within months following infant immunization. This generic observation remains unexplained. Here, we have analyzed the induction and organ‐localization of antigen‐specific IgG antibody‐secreting cells (ASC) following immunization of 1‐week‐old or adult BALB/c mice with tetanus toxoid (TT), a T‐dependent antigen. Early life priming induced only slightly lower numbers of TT‐specific IgG ASC in the spleen, and these reached adult levels following repeat immunization. In contrast, early life immunization generated much fewer bone marrow plasma cells than in adults, even after boosting. A similar limitation of the natural development of the bone marrow pool of ASC was observed. Transfer experiments with adult or early life spleen ASC indicated limited homing of TT‐specific adult ASC to the bone marrow of 4‐week‐old mice as compared to adult recipients, whereas homing patterns were similar when early life or adult ASC were transferred into adult recipients. These observations suggest that a limited bone marrow B cell homing capacity and, as a result, relatively deficient bone marrow ASC responses, are critical factors which may explain the limited persistence of IgG antibodies to T‐dependent antigens in early life.
A significant resurgence of early cases of pertussis is being observed in infants too young to have yet completed their three-dose vaccination schedule. In this study, murine models of immunization and Bordetella pertussis challenge were adapted to early life. This allowed comparative evaluation of immunogenicity and protective efficacy of immunization initiated in the neonatal period (7-day-old mice) or in infancy (3-week-old mice) with diphtheria-tetanus-whole-cell pertussis (DTPw) and diphtheria-tetanus-acellular pertussis (DTPa) vaccines. Neonatal DTPa vaccination induced strong pertussis-specific antibody and memory responses. Patterns of bacterial clearance were similar in both age groups. In contrast, as observed in human neonates, neonatal DTPw priming did not induce significant antibody responses to pertussis toxin (PT) and filamentous hemagglutinin (FHA) and even interfered with subsequent antibody responses. However, this did not reflect induction of permanent neonatal tolerance, as antigen-specific antibodies could be elicited by subsequent exposure to DTPa. Furthermore, despite these blunted PT and FHA antibody responses, the protective efficacy of DTPw in neonatal mice proved similar to that in infant mice, resulting in complete bacterial clearance at day 8 after B. pertussis challenge. Thus, neonatal priming with antipertussis vaccines should be considered to reduce the window of vulnerability to pertussis at the time of its greatest severity.Respiratory infection of young children with Bordetella pertussis causes whooping cough, a severe disease that is prevalent worldwide. Despite the administration of three doses of diphtheria-tetanus-pertussis vaccine (DTP) to 80% of children worldwide before their first birthday, recent World Health Organization (WHO) estimates indicate that whooping cough still annually affects up to 40 million children and results in 360,000 deaths (18). Although most of these infant deaths occur in developing countries, a significant shift of morbidity incidence towards young infants is also being observed in industrialized countries. In Canada, 78.9% of pertussis cases reported in 1999 were in children less than 6 months of age (with a median age of 12.4 weeks), and complications such as pneumonia, seizures, encephalopathy, and even death (0.9%) were common in this age group (16). Similar observations were reported in other countries with high pertussis vaccine coverage, attesting to an increased relative risk for infants too young to have yet completed their three-dose vaccination schedule (5,11,17,31,36,38,39).New vaccine strategies are being considered to further improve pertussis control during the first months of life. Administration of adolescent and adult boosters is currently under discussion, with the hope of reducing the adult reservoir of B. pertussis (7, 10). However, this universal adult booster strategy is challenged by considerable logistic issues and high costs. In addition, the evaluation of the impact of an adult booster strategy on early infant disease ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.