Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals.
Recent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-alpha, and stromal cell-derived factor-1alpha as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements. As shown in IL-6-deficient mice, IL-6 is required for a normal induction, but not for the maintenance of plasma cell responses in vivo, indicating that the effects of individual survival factors are redundant. Optimal survival of isolated plasma cells requires stimulation by a combination of factors acting synergistically. These results strongly support the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1alpha, TNF-alpha, and ligands for CD44, provides an environment required to mediate plasma cell longevity.
Cassese
Giuliana
G
Department for Humoral Immunology, Deutsches Rheumaforschungszentrum Berlin, Berlin, Germany.
Arce
Sergio
S
Hauser
Anja E
AE
Lehnert
Katja
K
Moewes
Beate
B
Mostarac
Miro
M
Muehlinghaus
Gwendolin
G
Szyska
Martin
M
Radbruch
Andreas
A
Manz
Rudolf A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000917:Antibody Formation / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002469:Cell Separation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000502:physiology; D015848:Interleukin-5 / Q000172:deficiency / Q000235:genetics; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015848:Interleukin-5; D015850:Interleukin-6