A combination of IL-10 and direct contact with plasma cell tumors decreases CD23 expression on splenic B cells.
We and others have previously found that splenic B cells from plasma cell tumor-bearing mice exhibit decreased CD23 expression. In the present study we further examined the mechanism of CD23 down-regulation by plasma cell tumors. We show here that although direct contact is required between the tumor cells and B cells, it is not sufficient, since fixed tumor cells do not induce the same reduction in CD23 expression. We have identified IL-10, a cytokine produce by the tumors, as the sole soluble factor that contributes to decreased CD23 expression on B cells induced by plasma cell tumors because 1) Abs to IL-10 prevent the loss of CD23 induced by plasma cell tumors both in vitro and in vivo; 2) engineered IL-10 negative variants of these tumors are reduced in their ability to down-regulate CD23 expression; 3) rIL-10 alone induces partial, but significant, decreases in CD23 expression on normal splenic B cells; and 4) the addition of IL-10 and fixed tumor cells to cultures of normal splenocytes decreases CD23 expression to levels similar to those in cocultures with live tumor cells. Collectively, these results demonstrate that plasma cell tumors down-regulate CD23 expression on B cells by a coordinate mechanism of IL-10 plus contact-mediated events and reveal a novel role for IL-10 in the regulation of CD23 expression on B cells that is suggestive of host B cell activation in the presence of the tumor.
Ruzek
M C
MC
Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.
Billadeau
D
D
Mathur
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010954:Plasmacytoma / Q000276:immunology*; D017455:Receptors, IgE / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D017455:Receptors, IgE; D016753:Interleukin-10