Linking age-related defects in B lymphopoiesis to the aging of hematopoietic stem cells

B cell genesis declines with age, but at what stage and why remains unclear. Previous studies attribute the decline in B cell production in aged mice to both environmental and cell-intrinsic defects that impact mid-to-late stream B cell precursors. However, mounting evidence suggests that the aging process may also negatively affect the earliest phases of B cell development. We review past studies on the B cells and aging question, discuss recent data suggesting that age-associated defects in B cell development reflect deficiencies in hematopoietic stem cell-proximal progenitor pools, and provide an integrative model that will hopefully facilitate further studies into this complex problem.