Although resting B cells as APC are tolerogenic for naive T cells in vivo,
we show here that they can provide all the costimulatory signals necessary
for naive T cell proliferation in vivo and in vitro. In the absence of an a
ctivating signal through the B cell Ag receptor, T cell proliferation after
Bg recognition on resting B cells depends on CD40 expression on the B cell
s, implying that naive T cells use the membrane-bound cytokine, CD40 ligand
(CD154), to induce the costimulatory signals that they need. Induction of
B7-1 (CD80) and increased or sustained expression of CD44H, ICAM-1 (CD54),
and B7-2 (CD86) are dependent on the interaction of CD40 ligand with CD40.
Transient expression (12 h) of B7-2 is T cell- and peptide Ag-dependent, bu
t CD40-independent. Only sustained (greater than or equal to 24 h) expressi
on of B7-2 and perhaps increased expression of ICAM-1 could be shown to be
functionally important in this system. T cells cultured with CD40-deficient
B cells and peptide remain about as responsive as fresh naive cells upon s
econdary culture with whole splenic APC, Therefore, B cells, and perhaps ot
her APC, may be tolerogenic not because they fail to provide sufficient cos
timulation for T cell proliferation, but because they are deficient in some
later functions necessary for a productive T cell response.