Manipulating B cell homeostasis: a key component in the advancement of targeted strategies.
Understanding the homeostatic mechanisms governing lymphocyte pools achieves critical importance as lymphocyte-targeted therapies expand in use and scope. The primacy of B lymphocyte stimulator (BLyS) family ligands and receptors in governing B lymphocyte homeostasis has become increasingly clear in recent years, affording insight into novel opportunities and potential pitfalls for targeted B cell therapeutics. Interclonal competition for BLyS-BR3 interactions determines the size of naïve B cell pools and can regulate the stringency of selection applied as cells complete maturation. Thus one of the predicted consequences of ablative therapies targeting primary pools is relaxed negative selection. This suggests that BLyS levels and B cell reconstitution rates may serve useful prognostic roles and that BLyS itself might be targeted to circumvent relapse. Alternatively, manipulations that allow rare, minimally autoreactive specificities to survive and mature may lead to opportunities in cases where antibody-based vaccine development has heretofore been unsuccessful. BLyS family ligands and receptors also play a role in activated and memory B cell pools, suggesting they might likewise be targeted to promote or delete particular antigen-experienced subpopulations in a similar way.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Laura S
LS
Treml
William J
WJ
Quinn
John F
JF
Treml
Jean L
JL
Scholz
Michael P
MP
Cancro
D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology / Q000378:metabolism*; D053301:B-Cell Maturation Antigen / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D051193:Toll-Like Receptors; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13