Impaired regeneration of the peripheral B cell repertoire from bone marrow following lymphopenia in old mice

Abstract

Aging is associated with a decreased production of B cells by the bone marrow and an increased life-span of peripheral B cells. To determine whether the decreased bone marrow B cell production is linked to the increased life-span of B cells in old mice, B cell regeneration following lymphopenia was studied in young and old mice. The rate of bone marrow pre-B cell and of splenic B cell regeneration is slower in irradiated, old compared to irradiated, young recipients of young, congeneic bone marrow. This finding reflects an age-associated defect in the bone marrow microenvironment. As the bone marrow is the only source of a diverse population of B cells, we measured the diversity of the splenic B cell repertoire regenerated following drug-induced lymphopenia in old and young mice. The heterogeneity of mRNA size from IgH complementarity determining region 3 (CDR3) was more restricted in splenic B cells from old compared to young mice providing additional evidence for an age-associated impairment in B cell production by the bone marrow.