Ageing Adversely Affects the Migration and Function of Marginal Zone B Cells

Marginal zone (MZ) B cells are positioned within the spleen to capture blood-borne Ag and immune complexes and deliver them to follicular dendritic cells in the B cell follicles. We show that within the spleens of aged mice antigen (Ag) capture by MZ B cells, and their ability to shuttle between the follicle and MZ were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine 1-phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T cell-independent (TI) antibody-responses to microbial polysaccharide Ag. In aged mice the ability to produce immunoglobulins in response to the TI-type 1 Ag, TNP-LPS, was impaired. These ageing related changes to the MZ and MZ B cells have implications for the clearance of blood-borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI Ag, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing-related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.