BCMA is essential for the survival of long-lived bone marrow plasma cells.
Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by interleukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this alpha-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor-immunoglobulin treatment, inhibited PC survival in vitro and in vivo. Heightened expression of B cell maturation antigen (BCMA), and lowered expression of transmembrane activator and cyclophilin ligand interactor and BAFF receptor in PCs relative to resting B cells suggests a vital role of BCMA in PC survival. Affirmation of the importance of BCMA in PC survival was provided by studies in BCMA-/- mice in which the survival of long-lived bone marrow PCs was impaired compared with wild-type controls. These findings offer new insights into the molecular basis for the long-term survival of PCs.
O'Connor
Brian P
BP
Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA.
Raman
Vanitha S
VS
Erickson
Loren D
LD
Cook
W James
WJ
Weaver
Lehn K
LK
Ahonen
Cory
C
Lin
Ling-Li
LL
Mantchev
George T
GT
Bram
Richard J
RJ
Noelle
Randolph J
RJ
D000818:Animals; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D017931:DNA Primers; D008565:Membrane Proteins / Q000172:deficiency / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D017931:DNA Primers; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C490176:Tnfrsf17 protein, mouse; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha