B cells and aging: balancing the homeostatic equation.
The interplay of selective and homeostatic processes dominates the behavior of B lineage subsets following B cell antigen receptor (BCR) expression, and extends to determinants of immune response quality and the persistence of immunologic memory. A key concept emerging from these considerations is that primary events acting upstream of mature B lymphocyte pools can profoundly impact downstream populations as the system attempts homeostatic adjustments. Since, advancing age is accompanied by profound changes in B cell generation and homeostasis, establishing the relative contributions of primary lesions versus compensatory homeostatic processes is critical to understanding these perturbations. Exploration of this problem requires an understanding of: (1) the identity, dynamics, and progenitor/successor relationships of marrow and peripheral B cell subsets; (2) the nature and interactions of selective and homeostatic processes acting in these subsets; (3) how these change with age. Our data show that BLyS and its receptors mediate peripheral B cell homeostasis, and that the size, dynamics and behavior of all B cell subsets influenced by B Lymphocyte Stimulator change with age. These findings suggest that homeostatic processes mediated through B Lymphocyte Stimulator are altered with age, and that these perturbations may primarily reflect compensatory homeostatic adjustments to upstream reductions in B cell generation.
Miller
Juli P
JP
University of Pennsylvania School of Medicine, 284 John Morgan Building, Department of Pathology and Laboratory Medicine, 36th and Hamilton Walk, Philadelphia, PA 19104-6082, USA.
Cancro
Michael P
MP
D000375:Aging / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology