Gene Expression in Transgenic Mice Expressing CD30L on T Cells

CD30L and CD30 are cell-surface glycoproteins in the TNF and TNFR superfamilies, respectively. Their expression is limited to immune cells and is tightly regulated. Cell surface expression of CD30 is restricted to subpopulations of activated T and B cells. CD30L is expressed primarily on activated T cells and subpopulations of B cells. The significance of CD30/CD30L interactions in immune regulation is not fully understood. Reported activities of CD30/CD30L in immune responses imply roles in regulation of secondary memory and antibody responses. Depending on the experimental system, both positive and negative regulation of immunoglobulin class switching and antibody production have been reported. Additionally, the biological activity of CD30/CD30L in animals has been difficult to assess due to the restricted and tightly regulated expression of this receptor-ligand pair. We generated transgenic mice with constitutive T cell specific overexpression of CD30L as a tool to help unravel the consequences of CD30/CD30L interactions in vivo. CD30L transgenic mice displayed a phenotype and responses to antigen challenge supporting a role for CD30/CD30L in promoting immunoglobulin class switching and antibody production. CD30L transgenic mice had increased numbers of germinal centers, elevated class-switched immunoglobulin isotypes, increased germinal center B cells and plasma cells, upregulation of genes indicative of B-cell activity, and exaggerated antibody responses to immune challenge. Interestingly, despite the heightened B-cell activity in CD30L transgenic mice, CD30L overexpression on T cells did not result in overt autoimmunity. Our results demonstrate that overexpression of CD30L on T cells promotes T cell-dependent B cell responses characterized by secondary antibody responses.

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