A SUBSET OF CD4(-CELLS CONTAINS PREFORMED CD40 LIGAND THAT IS RAPIDLYBUT TRANSIENTLY EXPRESSED ON THEIR SURFACE AFTER ACTIVATION THROUGH THE T-CELL RECEPTOR COMPLEX() MEMORY T)

Signaling through surface CD40 is essential for selecting B cells that have mutated their immunoglobulin variable region genes in germinal c enters and is an important signal in the early stages of antibody resp onses to T cell-dependent antigens. It is shown that a subset of CD45R O(+), CD4(+) T cells isolated from human tonsil contains preformed 30- 35-kD ligand for CD40. This is expressed on their surfaces within 5 mi n of their antigen-receptor complexes interacting with CD3 epsilon ant ibodies bound to ox erythrocytes. This surface expression does not req uire de novo protein synthesis and lasts for only 1-2 h. Preformed CD4 0 ligand (CD40L) was not detected in any CD4(+) CD45RA(+) T cells, but >90% of all CD4(+) T cells from the tonsil can be induced to express large amounts of CD40L on culture with phorbol myristate acetate and t he calcium ionophore ionomycin. This expression of CD40L starts betwee n 1 and 2 h, peaks at 6 h, and remains at a high level for >20 h. It i s totally prevented by adding a concentration of cycloheximide that in hibits CD25 synthesis by these activated cells. While CD3 epsilon anti body bound to ox red cells is a good inducer of surface expression of CD40L, it is a much less potent inducer of CD40L synthesis than phorbo l myristate acetate with ionomycin. Immunohistological analysis of ton sil sections shows that cells containing CD40L are located mainly in t he outer zone of germinal centers and the margins of the T zones that are rich in dendritic cells (interdigitating cells). The distribution of these cells is consistent with: (a) their interaction in T zones wi th B cells that have taken up and processed antigen and (b) their invo lvement in B cell selection in germinal centers.