CD30 is a CD40-inducible molecule that negatively regulates CD40-mediated immunoglobulin class switching in non-antigen-selected human B cells.
We used our monoclonal model of germinal center maturation, CL-01 B cells, to investigate the role of CD30 in human B cell differentiation. CL-01 cells are IgM+ IgD+ CD30+ and switch to IgG, IgA, and IgE when exposed to CD40L and IL-4. Switching is hampered by CD30 coengagement, possibly through interference with the CD40-mediated NF-kappaB-dependent transcriptional activation of downstream C(H) genes. The physiological relevance of this phenomenon is emphasized by similar CD30-mediated effects in naive B cells. Expression of CD30 by these cells is induced by CD40L but is inhibited by B cell receptor coengagement and/or exposure to IL-6 and IL-12. Our data suggest that CD30 critically regulates the CD40-mediated differentiation of non-antigen-selected human B cells.
Cerutti
A
A
Department of Pathology, Cornell University Graduate School of Medical Sciences, Cornell University Medical College, New York, New York 10021, USA.
Schaffer
A
A
Shah
S
S
Zan
H
H
Liou
H C
HC
Goodwin
R G
RG
Casali
P
P
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007072:Immunoglobulin D / Q000032:analysis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000032:analysis; D018664:Interleukin-12 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D016328:NF-kappa B / Q000494:pharmacology; D052002:NF-kappa B p50 Subunit; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D007070:Immunoglobulin A; D007127:Immunoglobulin Constant Regions; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D015850:Interleukin-6; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand; D018664:Interleukin-12; D007073:Immunoglobulin E