Inhibition of B cell growth factor (BCGF) by monoclonal antibodies directed against the C3d receptor (CR2)

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Abstract
Normal human B cell proliferation is controlled by various immunoregulatory signals including the T cell-derived lymphokine B cell growth factor (BCGF). Human BCGF provides the final proliferative signal to normal, activated B cells. We herein show that anti-CR2 monoclonal antibodies inhibit human B cell responsiveness to purified BCGF. Addition of anti-CR2 antibody, AB5, was capable of completely inhibiting BCGF-mediated enhancement of either anti-μ or staphylococcal protein A-activated human B cells (191 ± 21 cpm vs. 3942 ± 622 cpm, mean ± SEM). Inhibition of B cell response to BCGF by AB5 occurred in a dose-dependent manner. Monoclonal antibody anti-B2, which recognizes the same 140-kDa glycoprotein as AB5, in comparable concentrations also inhibited B cell responsiveness to BCGF. Monoclonal antibodies of the same subclass (IgG1) showed no inhibitory effect on BCGF enhancement of B cell proliferation. The F(ab')2 fragment of AB5 generated by pepsin digestion was similarly inhibitory as was the intact Ig. ABS-mediated inhibition was independent of the target B cell state of activation. Both resting and activated B cells (anti-μ or staphylococcal protein A activated) incubated with similar concentrations of AB5 were unresponsive to BCGF. The abilitv of anti-CR2 antibodies to block BCGF-dependent B cell proliferation suggests that occupancy of C3d membrane receptors may result in modulation of B cell proliferation in physiologic or clinical disease states.