Resting B lymphocytes as APC for naive T lymphocytes: dependence on CD40 ligand/CD40

DE Evans, MW Munks, JM Purkerson… - The Journal of …, 2000 - journals.aai.org
DE Evans, MW Munks, JM Purkerson, DC Parker
The Journal of Immunology, 2000journals.aai.org
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 …
Abstract
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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