Development of a high level of sustained borreliacidal antibody is paramount for maintaining protection against infection with Borrelia burgdorferi. We show that production of borreliacidal antibody can be enhanced by preventing the effects of gamma interferon (IFN-␥). When lymph node cells capable of producing borreliacidal antibody were cultured with anti-murine IFN-␥, an eightfold increase in borreliacidal antibody production was obtained. However, anti-IFN-␥ treatment of these cells also enhanced their ability to adaptively induce arthritis. When anti-IFN-␥-treated lymph node cells producing borreliacidal antibody were infused into C3H/HeJ mice and the mice were then challenged with B. burgdorferi, the mice developed severe destructive Lyme arthritis. Additional studies are needed to delineate the immune response responsible for the induction of arthritis and production of borreliacidal antibody. These studies are needed to ensure an effective and safe vaccine against infection with B. burgdorferi.Vaccination with Borrelia burgdorferi or its components can induce antibodies that prevent infection with the Lyme disease spirochete (1, 6, 8-10, 13, 27, 34). These vaccine-induced antibodies kill B. burgdorferi in the presence of complement (17,24). Specifically, it has been shown that antisera raised against recombinant outer surface protein OspA can prevent borrelial infection by passive immunization (8, 17, 31, 34), kill B. burgdorferi in vitro (13, 17, 18, 20, 24, 27, 29, 30), and sterilize B. burgdorferi-infected ticks (11). However, anti-OspA borreliacidal activity wanes rapidly after active immunization. Padilla et al. (24) reported that vaccination of experimental animals with recombinant OspA induced a borreliacidal antibody response that peaked 6 weeks after vaccination and declined rapidly. Moreover, human volunteers administered several doses of recombinant OspA produced borreliacidal antibody that rapidly decreased (24). Only one vaccinee had antibody 6 months after vaccination. The poor OspA-borreliacidal antibody response may have been a factor in prompting withdrawal of the vaccine for use in humans.Very little is currently known about the immunologic events that might promote and maintain a sustained borreliacidal antibody response after vaccination. Therefore, we developed an in vitro system to determine the effects of immunological mediators on production of borreliacidal activity. Several cytokines have been evaluated, including interleukin (IL)-4, a known B-lymphocyte stimulator (26), and its antagonist, gamma interferon (IFN-␥) (25). However, these cytokines failed to induce high levels of borreliacidal antibody (21, 22).Here, we report that treatment of lymph node cells containing borreliacidal antibody-producing cells with anti-murine IFN-␥ augments the production of anti-B. burgdorferi antibody. Unfortunately, treatment of these cells with anti-murine IFN-␥ also enhances their ability to induce arthritis.
MATERIALS AND METHODSMice. Inbred C3H/HeJ mice 8 to 12 weeks old were obtained fro...