Cutting edge: BLyS enables survival of transitional and mature B cells through distinct mediators.
These studies characterize BLyS responsiveness and receptor expression among transitional and mature peripheral B cells. The results show a maturation-associated increase in BLyS binding capacity that reflects differential expression patterns of the three BLyS receptors. Accordingly, BLyS administration enlarges only late transitional and mature peripheral B (MB) cell compartments. Furthermore, bromodeoxyuridine labeling and cell cycle analyses show these effects are mediated through enhanced proportional survival of cells traversing the T2, T3, and MB cell stages, rather than by causing proliferation or slowing transit within these subsets. Despite similar effects on survival, BLyS up-regulates the antiapoptotic genes A1 and bcl-x(L) in MB cells but not immature B cells. Together, these findings show that, while BLyS influences B cell survival in several peripheral differentiation subsets, the downstream mediators differ, thus providing the first direct evidence for an established B lineage survival system whose intermediates change as B cells mature.
Hsu
Benjamin L
BL
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Harless
Susan M
SM
Lindsley
R Coleman
RC
Hilbert
David M
DM
Cancro
Michael P
MP
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D053264:B-Cell Activating Factor; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation / Q000276:immunology; D051020:bcl-X Protein
D000276:Adjuvants, Immunologic; D053264:B-Cell Activating Factor; C096816:BCL2-related protein A1; C494812:Bcl2l1 protein, mouse; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein