The Role of B Cells and Accessory Cells in the Neonatal Response to TI-2 Antigens

Abstract

The neonate has an increased susceptibility to infection, in part owing to an inability to produce antibody to thymus-independent antigens such as bacterial polysaccharides (PS). This poor response to PS antigens is likely owing to multiple factors. Neonatal B cells are of an immature phenotype, as evidenced by cell-surface marker characteristics and increased susceptibility to tolerance induction. The spleen of the neonate has a different cellular composition, which is most prominent in the marginal zone. Neonatal accessory cells such as macrophages and dendritic cells (DCs) appear to produce less stimulatory cytokines and an overabundance of inhibitory cytokines. This review examines the current data supporting the role of B cells and accessory cells in the neonatal unresponsiveness to PS antigens.

Impaired B Cell Receptor Signaling Is Responsible for Reduced TACI Expression and Function in X-Linked Immunodeficient Mice

“…Moreover, similar to results obtained in the current study with XID B cells, we have shown previously that unlike adult B cells, crosslinking of the BCR on newborn B cells does not increase TACI expression (28). Consequently, as in XID mice, impaired BCR-induced NF-kB pathway activation may be responsible for the severely reduced TACI expression in newborn mice (66,69,71,72). Similarly, both newborn and XID B cell BAFF-R levels are comparable to their respective control mice, suggesting that in both mice, the pathway responsible for controlling BAFF-R expression remains functional and is not dependent on NF-kB.…”

Human immune system mice: current potential and limitations for translational research on human antibody responses

“…HIS mice up to 6 months of age give the same results (not shown) indicating that the length of the reconstitution period is not a factor. This is reminiscent of human infants and young children that do not respond well to polysaccharide (PS) vaccines [65][66][67]. While the protective antibody response to B. hermsii in mice is a TI response, it is targeted to bacterial surface proteins and is augmented by Toll-like receptor engagement [63,68].…”

“…Collectively, these observations lead us to hypothesize that HIS mice generated using our current protocol, like human infants and children [65][66][67], fail to respond to purified PS antigens due to incomplete development of the B cell compartment. In addition, although HIS mice can control B. hermsii infection, they do so less efficiently than wild type mice.…”

IL-7–Dependent B Lymphocytes Are Essential for the Anti-polysaccharide Response and Protective Immunity toStreptococcus pneumoniae

“…Impaired responses in neonates (9-12 d old) to TI-2 Ags can be attributed to the lack of MZ B cells (8,14). However, 3 to 4-wk-old mice are still unable to respond to TI Ags (7), despite having a developed MZ B cell compartment (Table I).…”

“…Similar to young children, young mice under the age of 4 wk are impaired in TI-2 responses (7). Possible factors that may account for the impaired TI responses in the young include defects in B cell activation and the lack of appropriate B cell subsets (8)(9)(10)(11)(12)(13)(14)(15)(16).…”