Inhibition of B cell growth factor (BCGF) by monoclonal antibodies directed against the C3d receptor (CR2).
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-mu 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. AB5-mediated inhibition was independent of the target B cell state of activation. Both resting and activated B cells (anti-mu or staphylococcal protein A activated) incubated with similar concentrations of AB5 were unresponsive to BCGF. The ability 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.
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D006131:Growth Inhibitors; D006801:Humans; D015847:Interleukin-4; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000037:antagonists & inhibitors*; D011951:Receptors, Complement / Q000276:immunology*; D017464:Receptors, Complement 3d
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D008222:Lymphokines; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; D015847:Interleukin-4