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 ce lls, 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 wh en exposed to CD40L and IL-4. Switching is hampered by CD30 coengageme nt, possibly through interference with the CD40-mediated NF-kappa B-de pendent transcriptional activation of downstream C-H genes. The physio logical relevance of this phenomenon is emphasized by similar CD30-med iated effects in naive B cells. Expression of CD30 by these cells is i nduced by CD40L but is inhibited by B cell receptor coengagement and/o r exposure to IL-6 and IL-12. Our data suggest that CD30 critically re gulates the CD40-mediated differentiation of non-antigen-selected huma n B cells.