Irradiation up-regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells
Article first published online: 30 APR 2004
Volume 112, Issue 2, pages 219–227, June 2004
How to Cite
Torihata, H., Ishikawa, F., Okada, Y., Tanaka, Y., Uchida, T., Suguro, T. and Kakiuchi, T. (2004), Irradiation up-regulates CD80 expression through two different mechanisms in spleen B cells, B lymphoma cells, and dendritic cells. Immunology, 112: 219–227. doi: 10.1111/j.1365-2567.2004.01872.x
- Issue published online: 30 APR 2004
- Article first published online: 30 APR 2004
- Received 15 October 2003; revised 17 February 2004; accepted 12 March 2004.
- B cells: irradiated, LPS-stimulated;
- CD80: up-regulation;
- NF-κB: nuclear factors;
- oxidative stress
We have previously demonstrated irradiation-induced up-regulation of CD80 expression in A20-HL B lymphoma cells by inducing expression of tumour necrosis factor-α (TNF-α) and CD154. In the present study, we investigated whether irradiation also up-regulates CD80 expression in mouse spleen B cells. Because freshly prepared spleen B cells are highly sensitive to irradiation, we employed spleen B cells stimulated with lipopolysaccharide (LPS-B cells). X-irradiation (8 Gy) followed by incubation (9–12 hr) highly and selectively up-regulated CD80 expression in LPS-B cells, whereas the same treatment slightly increased expression of CD54 and did not affect expression of CD86, major histocompatibility complex class II, CD11a or surface immunoglobulin M. The irradiation-induced up-regulation of CD80 expression resulted in enhanced APC function of LPS-B cells. Up-regulation of CD80 expression on LPS-B cells was accompanied by an increase in CD80 mRNA accumulation and nuclear factor (NF)-κB activation. Activation of NF-κB was shown to be critical for up-regulation of CD80 expression as pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, severely decreased the observed up-regulation. X-irradiation of LPS-B cells induced expression of TNF-α but not CD154. However, anti-TNF-α monoclonal antibody (mAb) with anti-CD154 mAb did not inhibit X-irradiation-induced up-regulation of CD80 expression in LPS-B cells, whereas these mAbs almost completely inhibited this up-regulation in A20-HL cells and bone marrow-derived dendritic cells (DCs). In contrast, a thiol antioxidant, N-acetyl-l-cysteine, completely blocked X-irradiation-induced up-regulation of CD80 expression in LPS-B cells, but not in A20-HL cells or in DCs. Based on these findings, we concluded that X-irradiation up-regulates CD80 expression not only in A20-HL cells and DCs but also in LPS-B cells, and that this up-regulation in LPS-B cells via NF-κB activation is dependent on the generation of reactive oxygen species, while that in A20-HL cells and DCs is not.