Repertoire of Antibody Response in Bone Marrow and the Memory Response Are Differentially Affected in Aging Mice

Abstract

The primary burst of Ab and germinal center (GC) formation in response to T-dependent Ag is compromised in aging mice. Here we examine the effects of aging on the post-GC phase of memory B cell differentiation and the late Ab repertoire maturation in bone marrow (BM) in mice immunized with a hapten nitrophenyl coupled to chicken γ-globulin. Specific Ab-forming cells (AFC) with mutated VH genes accumulated preferentially in the BM of aged mice, although the AFC numbers and average number of mutations per VH were lower, and the D gene usage was less restricted compared with those in the young animals. However, the repertoire of AFC after an Ag boost demonstrated the hallmarks of Ag selection, including the recurrent mutations and canonical VD rearrangements, similar to the late primary response in young animals. It is postulated that the Ab repertoire maturation in aged mice is delayed and may be notably improved by repeated immunizations.