Effects of anti-B7 monoclonal antibodies on humoral immune responses

The costimulatory interaction between CD28 on T cells and B7-related molecu les on antigen presenting cells plays an important role in a broad range of functions of the immune system, including protective immunity, tolerance i nduction, allograft rejection, and the development of autoimmune diseases. Monoclonal antibodies to B7-1 and B7-2 have been used in omo to examine the mechanisms underlying these processes and to evaluate costimulation antago nism as an approach to treatment of chronic autoimmune diseases. To determi ne whether anti-B7 mAb might elicit, or inhibit, a host immune response tha t could influence the effects of these antibodies in vivo, we assessed the immune response to rat anti-B7-1 and anti-B7-2 mAb in healthy (BALB/c) mice and in lupus-prone NZB/NZW F-1 (B/W) mice, in BALB/c mice, low doses (1-10 mu g) of mAb to B7-1 and mAb to B7-2 elicited brisk immune responses that occurred earlier and were significantly greater than the immune response to an isotype-matched control rat mAb to ovalbumin. In contrast, at higher do ses (100-500 mu g), both anti-B7 mAb, but not the control mAb, blocked the mouse anti-rat response. No such blockade occurred in B/W mice, who generat ed a significant mouse anti-rat response even at very high doses of anti-B7 mAb (1,000-4,000 mu g) Blockade of the immune response to the anti-B7 mAb in BALB/c mice apparently did not reflect generalized immune suppression, b ecause hi,oh doses of these mAb had little, if any effect on the humoral im mune response to another antigen. These findings indicate that: (1) mAb to B7-1 and B7-2 can elicit either a potent immune response or no immune respo nse at all depending upon the dose administered; (2) blockade of the immune response to anti-B7 mAb may be more difficult in the setting of autoimmuni ty; and (3) neither anti-B7-1 nor anti-B7-2 causes generalized suppression of humoral immunity. (C) 1999 Academic Press.