Integrating B cell homeostasis and selection with BLyS.
The mechanisms that maintain a pool of B cells that is adequately diverse yet devoid of pathogenic autoreactivity remain poorly understood. B cells complete maturation after migrating to the periphery, where they transit several intermediate developmental stages prior to recruitment into the long-lived primary pool. Since B lineage commitment is not coupled to peripheral B cell numbers and most mature peripheral B cells are quiescent, the sizes of mature peripheral compartments are primarily determined by the proportion of immature B cells that survive transit through later developmental stages, coupled with the longevity of mature B cells themselves. Compelling evidence indicates that the B cell antigen receptor (BcR) plays an essential role in all of these processes, but further findings indicate a similar role for the recently described tumor necrosis factor family member B lymphocyte stimulator (BLyS). Signaling through the BLyS receptor, Bcmd/BR3, controls B cell numbers in two ways: by varying the proportion of cells that complete transitional B cell development, and by serving as the primary determinant of mature B cell longevity. The striking congruence of BcR- and BLyS-mediated effects on B cell selection and survival suggests these pathways may be related. The recent discovery that BcR signaling is selectively coupled to Bcmd/BR3 expression links BcR- and BLyS-mediated activities in transitional and mature B cells, suggesting specificity-based selection and survival may be mechanistically similar processes.
Harless Smith
Susan
S
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cancro
Michael P
MP
D000818:Animals; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival; D006706:Homeostasis; D007156:Immunologic Memory / Q000502:physiology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha