Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1.

Abstract

The lymphokine B-cell stimulatory factor 1 (BSF-1) has been shown to greatly enhance the differentiation of lipopolysaccharide-activated B cells into IgGl-and IgEsecreting cells in vitro. To determine whether in vivo IgG1 and IgE antibody responses are BSF-1 dependent, the ability of a monoclonal rat IgG1 anti-BSF-1 antibody, 11B11, to affect polyclonal IgG1 and IgE production in mice infected with the nematode parasite Nippostrongylus brasiliensis or iIiected with a purified goat antibody to mouse IgD was studied. 11B11-containing ascites fluid or purified 11B11 strongly inhibited IgE production in both systems but did not affect IgG1 production, while control ascites or normal rat IgG1 had no IgE-inhibitory activity. These results indicate an important physiologic role for BSF-1 in the generation of IgE antibody responses and suggest means for limiting the production of antibodies responsible for allergic reactions without inhibiting protective antibody responses.IgE has a crucial role in the pathogenesis of allergic reactions (1, 2), is thought to be important for host elimination of helminthic parasites (3-5), and is produced in relatively large quantities by animals infected with these parasites (6)(7)(8)(9). The generation of IgE-secreting cells has been shown to be dependent upon helper T lymphocytes (10); no IgE secretion is seen in parasite-infected congenitally athymic (nude) mice (11, 12) or parasite-infected mice injected with a monoclonal antibody (anti-L3T4) (13) that blocks helper T-cell function (14). The nature of the T-cell help required for the generation of an IgE response in vivo is not certain, but soluble, T-cell-produced, IgE binding factors have been shown to modulate in vitro generated IgE responses (15). The demonstration that a purified murine T-cell lymphokine, B-cell stimulatory factor 1 (BSF-1)1 (17,18), is capable of inducing a greater than 100-fold increase in IgE secretion in vitro by lipopolysaccharide-activated mouse splenic B-cell blasts (19), suggested that this lymphokine might be important in the in vivo stimulation of IgE secretion. This led us to study whether a monoclonal anti-BSF-1 antibody was capable of inhibiting a mouse polyclonal IgE response to infection with the nematode parasite Nippostrongylus brasiliensis (Nb) or to injection of an affinity-purified goat anti-IgD (GaM8). Results of these studies indicate that anti-BSF-1 antibody substantially inhibits IgE but not IgG1 secretion in these mice and thus strongly suggest a specific and important role for BSF-1 in the physiologic stimulation of IgE responses.MATERIALS AND METHODS Animals. Female BALB/c and male athymic nude mice were obtained from the National Institutes of Health Small Animals Division (Bethesda, MD) and were used at 8-12 weeks of age.Antibodies. Affinity-purified GaM8 (20), rabbit antibody specific for the e chain of mouse IgE (RaME) (9), and alkaline phosphatase conjugated to affinity-purified, mouse serumabsorbed, goat anti-rabbit immunoglobulin (21) were prepared. The rat-mouse hybri...

Decision criteria for resolving isotype switching conflicts by B cells

“…Due to the ability of viruses to replicate quickly, presumably it is important to mount a rapid response to facilitate eradication as quickly as possible. In contrast, IL-4 appears to be involved in immune responses to helminthic parasites [32][33][34], which are generally much slower growing and may not require the same urgency of response. If the IFN-c response is dominant, this ensures that in the presence of concurrent parasitic and viral infections, the B cell will make a response that is appropriate for dealing with the more immediate problem of the virus.…”

Modulation of the Immune System by Listeria monocytogenes‐Mediated Gene Transfer into Mammalian Cells

“…MAb specific for IL-4 and IL-12 were provided by Dr. W.E. Paul, National Institutes of Health, Md., U.S.A., and by Dr. G. Trinchieri, Wister Institute, Pa., U.S.A. (7,32). Caco-2 cells and HepG2 cells were of human origin and were provided by Dr. C. Sasakawa, the University of Tokyo, Tokyo, and Dr. S.M.F.…”

Preferential induction of a Th1 immune response and inhibition of specific IgE antibody formation by plasmid DNA immunization.

“…Although IgGl antibody production, like IgE production, is typical for a Th2 cell response (9), IgGl formation is much less dependent on, or in some instances even independent of, the requirement for IL-4. Injection of anti-IL-4 antibodies inhibits IgE but not IgGl formation in mice (19). Although the mechanism of the selective down-regulation of IgE antibody production is not known, it is probably due to the induction of new antigen-specific Th, cells that are able to down-regulate the differentiation of new Th2 cells as has been shown in other systems (9).…”