CD30 / CD30L interactions promote class-switched antibody responses to T-dependent antigens (34.3)

Abstract The cell-surface glycoproteins CD30 and CD30L are members of the TNFR and TNF superfamilies, respectively. CD30 is expressed on subpopulations of activated T and B cells. CD30L is expressed on activated T cells, macrophages, and dendritic cells, as well as germinal center B cells. CD30 / CD30L interactions provide activation-induced costimulatory signals that sustain T-cell responses, mediate B-cell activity, and generate long-lived memory T cells for chronic B-cell help. Although other activation-induced costimulatory molecules induce antibody isotype class switching, it is less clear what the function is of CD30 signaling on class switching and antibody production. Therefore, we tested the effect of in vivo blockade of the CD30 / CD30L pathway on antibody class switching in response to T-dependent antigens using two systems that require activated-T cells to stimulate B-cell responses. First, BALB/c mice immunized with a T-dependent antigen and treated with anti-CD30L antibodies produced less antigen-specific antibodies of IgG1 and IgE isotypes as compared to control-treated mice, whereas antigen-specific antibodies of the IgM isotype were similar in all groups. Likewise, NZB/W F1 lupus-prone mice treated with anti-CD30L antibodies produced less anti-dsDNA antibodies of the IgG1 and IgG2a isotypes as compared to control-treated mice, whereas anti-dsDNA antibodies of the IgM isotype were similar in all groups. In both systems, specific subpopulations of lymphocytes necessary for responses to T-dependent antigens were reduced by blockade of the CD30 / CD30L pathway. Our results demonstrate that CD30 / CD30L interactions positively regulate T-cell dependent B-cell responses necessary for class-switched antibody responses.