CD134L engagement enhances human B cell Ig production: CD154/CD40, CD70/CD27, and CD134/CD134L interactions coordinately regulate T cell-dependent B cell responses.
CD134 is a member of the TNFR family expressed on activated T cells, whose ligand, CD134L, is found preferentially on activated B cells. We have previously reported that the CD70/CD27 interaction may be more important in the induction of plasma cell differentiation after the expansion phase induced by the CD154/CD40 interaction has occurred. When CD134-transfected cells were added to PBMCs stimulated with pokeweed mitogen, IgG production was enhanced in a dose-dependent fashion. Addition of CD134-transfected cells to B cells stimulated with Staphylococcus aureus Cowan I strain/IL-2 resulted in little if any enhancement of B cell IgG production and proliferation. We found that while CD134-transfected cells induced no IgG production by themselves, it greatly enhanced IgG production in the presence of CD40 stimulation or T cell cytokines such as IL-4 and IL-10. The addition of CD134-transfected cells showed only a slight increase in the number of plasma cells compared with that in the culture without them, indicating that an increased Ig production rate per cell is responsible for the observed enhancing effect of CD134L engagement rather than increase in plasma cell generation. These results strongly suggest different and sequential roles of the TNF/TNFR family molecules in human T cell-dependent B cell responses through cell-cell contacts and the cytokine network.
Morimoto
S
S
Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan.
Kanno
Y
Y
Tanaka
Y
Y
Tokano
Y
Y
Hashimoto
H
H
Jacquot
S
S
Morimoto
C
C
Schlossman
S F
SF
Yagita
H
H
Okumura
K
K
Kobata
T
T
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053282:CD27 Ligand; D023201:CD40 Ligand; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism* / Q000502:physiology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; C505772:Cd70 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D023201:CD40 Ligand