Cutting edge: the dependence of plasma cells and independence of memory B cells on BAFF and APRIL.
Memory B (B(MEM)) cells and long-lived bone marrow plasma cells (BM-PCs) persist within local environmental survival niches that afford cellular longevity. However, the factors supporting B(MEM) cell survival within the secondary lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly characterized. We report herein that long-lived B(MEM) cell survival and function are completely independent of BAFF (B cell-activating factor of the TNF family) or APRIL (a proliferation-inducing ligand). Thus, B(MEM) cells represent the only mature B2 lineage subset whose survival is independent of these ligands. We have previously shown that the TNFR family member receptor BCMA (B cell maturation Ag) is a critical survival receptor for BM-PC survival in vivo. We identify in this study the ligands critical for BM-PC survival and show that either BAFF or APRIL supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL-dependent and -independent components of long-lived humoral immunity.
Benson
Micah J
MJ
Department of Microbiology and Immunology, Dartmouth Medical School, The Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
Dillon
Stacey R
SR
Castigli
Emanuela
E
Geha
Raif S
RS
Xu
Shengli
S
Lam
Kong-Peng
KP
Noelle
Randolph J
RJ
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D053264:B-Cell Activating Factor / Q000378:metabolism / Q000502:physiology*; D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D053301:B-Cell Maturation Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000096:biosynthesis / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; C486361:Tnfrsf13b protein, mouse; C491959:Tnfsf13 protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13