Isolation of cDNAS encoding T-BAM, a surface glycoprotein on CD4⁺ T cells mediating contact-dependent helper function for B cells: Identity with the CD40-ligand

"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4⁺ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH₂-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH₂-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4⁺ and on few if any CD8⁺ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4⁺ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8⁺ T cells after activation. Importantly, a subset of CD8⁺ T cells do not express T-BAM after activation and this T-BAM^- phenotype is maintained on certain CD8⁺ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.