Activation and Fixation of C3 by Human B Cell Lines Is Enhanced by Interferon-Gamma and Tumor Necrosis Factor Alpha

Abstract

Human B cell lines were tested for the capacity to convert C3 to C3b/iC3b through the alternative C pathway (ACP) and to fix the generated C3 fragments. The panel of lines included four Epstein-Barr virus (EBV)-negative Burkitt’s lymphomas and their sublines converted with two EBV strains: the prototype B958 (B virus) and the nontransforming P3HR-1 (P virus). Comparison of these groups of parallel lines (derived from a single patient) showed that the EBV-carrying cells were more efficient in activation and fixation of C3. All cell lines activated C3 with higher efficiency when treated with interferon gamma or tumor necrosis factor alpha. After treatment, the comparative relationships between the sublines changed. The treated EBV-negative and the P virus converted sublines showed similar levels of ACP activation, while the B virus carrying sublines were more efficient. The amounts of bound C3 fragments on the activating cells correlated with the ACP efficiencies. In accordance with the elevated ACP activation capacity of the cells after cytokine treatment, the amounts of C3 fragments detected on their surfaces were higher. Among the lines tested, only two (BL28 and Ramos) were sensitive to C-mediated lysis. The lytic sensitivity of these two lines increased after treatment with the cytokines. The results indicate, therefore, that the cytokine-induced increase in ACP activation by Burkitt’s lymphoma lines is not sufficient to overcome resistance to C lysis.

Regulation of Alternative Pathway Activation and C3a Production by Adipose Cells

“…It is not known what, if any, complement regulatory proteins are expressed by adipocytes or adipose tissue. It is not known whether differential expression of TNF-a in adipose tissue in lean vs. obese mice has an effect on expression of local complement regulators or the level of C3a production in vivo; TNF-a has been shown to promote complement activation on various cells in vitro (8,39,46). The previous data on the decreased levels of factor D activity in obese mice (41) and decreased levels of fmed C3 activation fragments in obese adipose tissue (8) suggest that C3a levels may be decreased in obese mice, which seems paradoxical if this peptide has triglyceride synthesis stimulating activity.…”