TY - JOUR
T1 - CD30 signaling negatively regulates CD40-induced immunoglobulin class switching in human B cells. A mechanism for preferential differentiation of antigen selected germinal center B cells
AU - Cerutti, Andrea
AU - Schaffer, Andras
AU - Zan, Hong
AU - Liou, Hsiou Chi
AU - Casali, Paolo
PY - 1998/3/20
Y1 - 1998/3/20
N2 - Triggering of B cell Ag receptor (BCR) and CD40 provides the main drive for human B cell germinal center (GC) proliferation and differentiation. BCR signaling is negatively regulated by B cell surface inhibitory molecules, the lack of which can lead to uncontrolled B cell clonal expansion in response to antigenic stimulation. As for CD40, no surface inhibitory molecules have been so far identified. We have used our recently identified monoclonal model of GC B cell differentiation, IgM+ IgD+ CD30+ CL-01 cells, to investigate the role of CD30 in human B cell maturation. CL-01 cells switch to IgG, IgA, and IgE in response to CD40L and IL-4. This switching is effectively hampered by coengagement of CD30 by an agonistic mAb, possibly through interference with the CD40-mediated NF-κB-dependent transcriptional activation of downstream Cγ, Cα, and C∈ genes. The physiological relevance of CD30-mediated inhibition of Ig class switching is emphasized by similar CD30-mediated effects in freshly isolated naive B cells. Effective expression of CD30 by these cells is induced by engagement of CD40 by CD40L, but is inhibited by BCR coengagement. These findings indicate that CD30 negatively modulates CD40-induced Ig class switching, and suggest that CD30 plays a major role in the regulation of human B cell GC differentation.
AB - Triggering of B cell Ag receptor (BCR) and CD40 provides the main drive for human B cell germinal center (GC) proliferation and differentiation. BCR signaling is negatively regulated by B cell surface inhibitory molecules, the lack of which can lead to uncontrolled B cell clonal expansion in response to antigenic stimulation. As for CD40, no surface inhibitory molecules have been so far identified. We have used our recently identified monoclonal model of GC B cell differentiation, IgM+ IgD+ CD30+ CL-01 cells, to investigate the role of CD30 in human B cell maturation. CL-01 cells switch to IgG, IgA, and IgE in response to CD40L and IL-4. This switching is effectively hampered by coengagement of CD30 by an agonistic mAb, possibly through interference with the CD40-mediated NF-κB-dependent transcriptional activation of downstream Cγ, Cα, and C∈ genes. The physiological relevance of CD30-mediated inhibition of Ig class switching is emphasized by similar CD30-mediated effects in freshly isolated naive B cells. Effective expression of CD30 by these cells is induced by engagement of CD40 by CD40L, but is inhibited by BCR coengagement. These findings indicate that CD30 negatively modulates CD40-induced Ig class switching, and suggest that CD30 plays a major role in the regulation of human B cell GC differentation.
UR - http://www.scopus.com/inward/record.url?scp=33749322986&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749322986&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33749322986
VL - 12
SP - A1056
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 5
ER -