Dose-dependent variation in the response to anti-b7 antibodies: low doses elicit a potent immune response while high doses block the immune response

Monoclonal antibodies (mAb) to B7-1 and B7-2 have been used in vivo to examine the role of these ligands in T cell costimulation in normal and autoimmune mice. To determine whether in vivo treatment with B7 mAb might have significant effects on the immune response to these mAb, we assessed the immune response of BALB/c mice to isotype-matched (rat IgG2a) anti-B7-l and anti-B7-2 mAb. Eight-week-old BALB/c females received six weekly ip injections of either 1 μg, 10 μg, 100 μg or 500 μg of anti-B7-1, anti-B7-2 or a control rat IgG2a anti-ovalbumin mAb (OVA). At the two lowest doses, the immune response to both anti-B7 mAb was enhanced relative to the control mAb; it occurred immediately (mean titer one week after a single 10 μg dose was 1:50 and 1:256 for ant-B7-l and anti-B7-2, respectively, compared to no response to the control antibody), and it remained significantly greater (mean titer after 6 weeks of the 10 μg dose was l:256foranti-B7-l and 1:40% foranti-B7-2, compared to, 1:32 for anti-OVA; p<0.01 for all comparisons). In contrast, at high doses, both anti-B7 mAb blocked the mouse anti-rat mAb response (mean titer after 6 weeks of the 500 μg dose was undeteclable for both anti-B7 mAb, compared to 1:400 for the control mAb; p<0.01). These results imply that at low doses, which may be insufficient to block B7-T cell interactions, anti-B7 mAb may augment immune responses, perhaps through direct effects on B cells and APC. In contrast, at high doses, the anti-B7 mAb block immune responses by inhibiting T cell costimulation. These findings have implications regarding the interpretation of studies using anti-B7 mAb.