Abstract
B7 family molecules expressed on antigen-presenting cells stimulate or inhibit normal immune responses. The aim of this study was to investigate whether functional B7.2 and B7-H2 molecules are expressed on myeloma cells and, if so, whether they are associated with pathophysiology in myeloma. The expression of B7.2 and B7-H2 molecules on normal plasma and neoplastic (myeloma) plasma cells was analyzed. The cell proliferation and immunomodulatory function of myeloma cells related to B7.2 and B7-H2 expression were examined. Human myeloma cell lines commonly expressed B7.2 and B7-H2 molecules. B7.2 expression on plasma cells was more common in myeloma patients (n = 35) compared with that in patients with monoclonal gammopathy of unknown significance (n = 12) or hematologically normal individuals (n = 10). Plasma cells expressing B7-H2 were observed in myeloma patients alone, although rarely. Patients whose myeloma cells showed high B7.2 expression were more anemic and thrombocytopenic than other myeloma patients. The expression of these molecules was induced or augmented by cultivating myeloma cells with autologous stroma cells or tumor necrosis factor-alpha, a key cytokine in myeloma biology. Cell proliferation was more rapid in the B7.2+ and B7-H2+ populations compared with the B7.2(-) and B7-H2(-) populations, respectively, in the human myeloma cell lines examined. B7.2 and B7-H2 molecules on myeloma cells induced normal CD4+ T cells to proliferate and produce soluble factors, including interleukin-10 that stimulate myeloma cell proliferation. Functional B7.2 and B7-H2 molecules detected on myeloma cells may be involved in the pathophysiology of myeloma.
Highlights
B7 family molecules expressed on antigen-presenting cells stimulate or inhibit normal immune responses
We investigated whether functional B7.2 and B7-H2 molecules are expressed on myeloma cells and, if so, whether these B7 molecules are associated with pathophysiology in MM
We examined whether cytokines, i.e., tumor necrosis factor-a (TNF-a), IL-6, or IL-10, affect B7.2 and B7-H2 expression in five human myeloma cell lines (HMCL)
Summary
B7 family molecules expressed on antigen-presenting cells stimulate or inhibit normal immune responses. The aim of this study was to investigate whether functional B7.2 and B7-H2 molecules are expressed on myeloma cells and, if so, whether they are associated with pathophysiology in myeloma. The B7 family molecules play an important role in the immune response by costimulating or coinhibiting T cells via antigen – T-cell receptor interactions (13 – 16). B7 family molecules are expressed on professional antigen-presenting cells and on some tumor cells and the latter may modulate antitumor immunity in hosts. Pope et al [22] observed that MM patients whose tumor cells expressed B7.2 molecules had a poor prognosis They did not examine whether the B7.2 molecules on myeloma cells were functional. We investigated whether functional B7.2 and B7-H2 molecules are expressed on myeloma cells and, if so, whether these B7 molecules are associated with pathophysiology in MM
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