Age-Related Decline of B1-Like Cells and Natural Antibodies: Implications for Pneumococcal Susceptibility 9069

Abstract Description B1 cells, a distinct lineage of B cells, produce natural antibodies in the absence of infection or vaccination. However, with advancing age, B1 cells decline in number, reduce antibody secretion, and lose antigenic diversity. Phosphorylcholine (PC) is a ubiquitous antigen expressed on several microbial pathogens including Streptococcus pneumoniae. PC-specific natural antibodies are particularly important in providing protection against Streptococcus pneumoniae. While younger individuals maintain robust PC-specific natural antibody levels, older adults exhibit a marked reduction in these antibodies. In this study, we investigated the behavior of PC-specific human B1 cells. Initial attempts to identify PC-specific B1 cells using PC-BSA-FITC led to non-specific recruitment due to binding the carrier protein or FITC fluorophore. To overcome this, we developed a dual-staining method using PC-BSA-FITC and PC-OVA-A647. Analysis of B cells from the peripheral blood of young and older healthy volunteers revealed that PC-specific B1 cells decline with age, paralleling the overall decline in B1 cells, despite the importance of the antigen target. Our findings highlight that the age-related decline in B1 cells and B1 cell-derived natural antibodies is a likely factor in the increased susceptibility of older adults to pneumococcal infections. These insights provide a foundation for developing strategies to restore natural antibodies and improve immune defenses in aging populations. Funding Sources NIH R01AI142004 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)