Homeostatic control of B lymphocyte subsets.
Lymphocyte homeostasis poses a multi-faceted biological puzzle, because steady pre-immune populations must be maintained at an acceptable steady state to yield effective protection, despite stringent selective events during their generation. In addition, activated, memory and both short- and long-term effectors must be governed by independent homeostatic mechanisms. Finally, advancing age is accompanied by substantial changes that impact the dynamics and behavior of these pools, leading to cumulative homeostatic perturbations and compensation. Our laboratory has focused on the over-arching role of BLyS family ligands and receptors in these processes. These studies have led to a conceptual framework within which distinct homeostatic niches are specified by BLyS receptor signatures, which define the BLyS family ligands that can afford survival. The cues for establishing these receptor signatures, as well as the downstream survival mechanisms involved, are integrated with cell extrinsic inputs via cross talk among downstream mediators. A refined understanding of these relationships should yield insight into the selection and maintenance of B cell subsets, as well as an appreciation of how homeostatic mechanisms may contribute to immunosenescence.
Crowley
Jenni E
JE
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 284 John Morgan Building 36th and Hamilton Walk, Philadelphia, PA, 19104-6082, USA.
Scholz
Jean L
JL
Quinn
William J
WJ
Stadanlick
Jason E
JE
Treml
John F
JF
Treml
Laura S
LS
Hao
Yi
Y
Goenka
Radhika
R
O'Neill
Patrick J
PJ
Matthews
Andrew H
AH
Parsons
Ronald F
RF
Cancro
Michael P
MP
D000818:Animals; D053264:B-Cell Activating Factor / Q000502:physiology; D053265:B-Cell Activation Factor Receptor / Q000502:physiology; D053301:B-Cell Maturation Antigen / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D016922:Cellular Senescence / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000502:physiology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000502:physiology
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D011947:Receptors, Antigen, B-Cell; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13