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)
M. Casamayorpalleja et al., 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), The Journal of experimental medicine, 181(4), 1995, pp. 1293-1301
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.