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.
Quinn
William J
WJ
University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, 284 John Morgan Building, 36th And Hamilton Walk, Philadelphia, PA 19104-8062, USA.
Scholz
Jean L
JL
Cancro
Michael P
MP
D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D016922:Cellular Senescence / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology; D006706:Homeostasis / Q000276:immunology*; D006801:Humans