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Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97201
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 activating signal through the B cell Ag receptor,
T cell proliferation after Ag recognition on resting B cells depends on
CD40 expression on the B cells, 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, but CD40-independent. Only sustained (
24 h) expression
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 secondary culture with whole splenic APC. Therefore, B
cells, and perhaps other APC, may be tolerogenic not because they fail
to provide sufficient costimulation for T cell proliferation, but
because they are deficient in some later functions necessary for a
productive T cell response.
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