An underdeveloped or impaired immune response in young children is associated with increased susceptibility to Streptococcus pneumonia (Spn) infections. We determined serum antibody titers against 3 Spn vaccine candidate proteins and vaccine serotype polysaccharide antigens in a group of Spn infection prone 9-18months old and found lower IgG antibody titers to all tested antigens compared to age-matched non-infection-prone children. We also found the children had significantly reduced percentages of total memory B-cells, switched memory B-cells and plasma cells. We sought a mechanistic explanation for that result by examination of TNF family receptors (TNFRs) TACI, BCMA, and BAFFR receptor expression on B-cells and found significantly lower BAFFR and TACI expression; significantly lower proliferation of B-cells stimulated with exogenous BAFF; and diminished expression of co-stimulatory receptors B7-1 and B7-2 among infection prone vs. non-prone children. We conclude that lower expression of TNFRs, lower proliferation of B-cells in response to BAFF and lower expression of B7-1 and B7-2 by B-cells may contribute to reduced antibody responses to Spn and consequent infection proneness in young children.
【저자키워드】 acute otitis media, B-cell activating factor receptor, B-cell maturation antigen, Calcium-modulator, Cytophilin ligand interactor, Transmembrane activator,