Dwindling competition with constant demand: Can homeostatic adjustments explain age-associated changes in peripheral B cell selection?

The close relationship between specificity-based selection and homeostatic processes in maintaining peripheral B cell pools has become increasingly evident. Thus, age-associated changes observed within these pools may reflect homeostatic responses to proximal primary lesions. Marked shifts in the size and dynamics of most B lymphocyte subsets and their progenitors occur with age: perturbations in B lineage precursors result in reduced production of immature B lymphocytes in the bone marrow and transitional pools in the periphery, but these effects appear to be offset by compensatory homeostatic processes at the marrow-periphery interface. We propose a model whereby these “distal” homeostatic adjustments relax the stringency of specificity based selection, affording a potential explanation for the increased frequency of autoreactive specificities with age.