Elsevier

Immunopharmacology

Volume 26, Issue 2, September–October 1993, Pages 105-112

Direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on responses to lipopolysaccharide (LPS) by isolated murine B-cells

https://doi.org/10.1016/0162-3109(93)90002-8Get rights and content

Abstract

Previous results from this laboratory have indicated that the B-cell is the primary cell target responsible for the suppression of humoral immunity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While other laboratories have confirmed that the B-cell is affected, there is not a clear understanding of TCDD's relative effects on B-cell proliferation and differentiation. In the present study, we isolated B-cells from the whole spleen cell suspensions from female B6C3F1 mice and further separated them according to density on a percoll density step gradient. Cell cycle analysis by propidium iodide indicated that both high (i.e., 1.092–1.079 density interface) and low (i.e., 1.079–1.070 density interface) density B-cells were predominantly cells in the G0/G1 phase of the cell cycle. Based on acridine orange staining, low-density B-cells exhibited slightly higher RNA levels than high-density B-cells indicating they are an “activated” population of cells, probably somewhere in G1A. Confirmation of these results was the observation that the high density, small, resting B-cells had negligible background proliferation and immunoglobulin secretion, while the low density, larger, activated B-cells had marked background proliferative and antibody responses. Direct addition of TCDD (0.3–30.0 nM) produced a significant, dose-related and comparable suppression of both parameters in the low density B-cells. Similar results were obtained when low density B-cells were stimulated with LPS and exposed to TCDD. In contrast, neither the proliferation nor the antibody response by high density B-cells stimulated with LPS were affected by TCDD. These findings demonstrate that the low density splenic B-cells are targets in suppression of antibody responses by TCDD, and that both proliferation and differentiation are coordinately affected.

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