C3-Dependence of B-Cell Activation?
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There is growing evidence that LPS are B cell mitogens, can substitute for T cells, and activate the alternate pathway of the C system (bypass), but the interdependence of these phenomena is unclear. Therefore the effect of other potent bypass-activators, especially CVF, was investigated with regard to the mentioned activities and the role of C3: 1) Purified, pyrogen-free CVF in its soluble form or coupled to Sepharose (Seph-CVF) as well as LPS (E. coli 0111:B4) are strongly mitogenic for B cells. In the presence of C3-sufficient but not C3-depleted fetal calf serum (FCS), lymph node cells (LNC) from congenitally athymic nude mice can be stimulated by CVF and Seph-CVF with a concentration optimum of 16 µg/ml (30-fold enhancement of the H3-Th. uptake). 2) Bypass-activating B cell mitogens can substitute for T cells in a T cell-dependent antibody response: Addition of LPS, CVF or most effectively Seph-CVF restores the potential of antibody formation to SRBC in B cell cultures, supplemented with macrophages or 2-mercapto-ethanol and FCS (50- to 100-fold rise in 19S plaque-forming cells).