Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1

Abstract

Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effects and direct anti-cancer effects of PSK have been reported. Most of studies describing the immunomodulatory effects focused on cellular immunity, although there were several studies which focused on humoral immunity where PSK was shown to be able to induce antibody production in vivo. However, even in these humoral immunity studies, it is thought that the enhancement of antibody production was due to the activation of cellular immunity. In this study, we investigated the direct effect of PSK on B cells and discovered that PSK was able to enhance IgM production in the human B cell line BALL-1. Furthermore, BALL-1 was shown to have the characteristic features of B-1a cells, which are independently involved in the primary immune response. These results show that there is a possibility that PSK directly acts on B cells and simultaneously enhances both humoral immunity and cellular immunity.

Introduction

Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effect of PSK have been reported. The studies focused on cellular immunity defined by the actions of cells such as T cells [1], macrophages in tumour bearing mice [2], and a natural killer cell line in vitro [3]. Several humoral immunity studies have shown that PSK induced antibody production in vivo [2], however, it is thought that enhancement of antibody production by PSK is mediated by the activation of cellular immunity [4]. Thus far, we have not found any reports describing the direct immunomodulatory effect of PSK on B cells although Hattori et al. reported that PSK induced apoptosis in the B cell line Namalwa which was used as a model of hematological malignant cells [5].

On the other hand, in our previous study, it was shown that the water extract of the parasitic plant Cistanche salsa (C.A. Meyer) G. Beck, Orobanchaceae was able to enhance production of IgM and IgG in human lymph node lymphocytes. Furthermore, its dialysate was able to enhance IgM production in the human B cell line BALL-1; in addition, it induced cell proliferation to small extent [6]. BALL-1 was originally obtained from the peripheral blood of a patient with acute lymphoblastic leukemia (ALL). BALL-1 is Epstein–Barr virus-determined nuclear antigen negative [7]. Uncommon for B cell lines, BALL-1 secretes interferon (IFN)-α and tumour necrosis factor (TNF)-α and TNF-β upon stimulation with the Japanese hemagglutinating virus [8]. Furthermore, our dialysate was shown to induce apoptosis in the Burkitt's lymphoma (BL) cell line Namalwa [9]. Likewise, PSK was reported to induce apoptosis in Namalwa as mentioned above. We therefore investigated the effect of PSK on BALL-1 and the characteristic features of BALL-1 to obtain indicators for future studies in vivo.