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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...

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B cell stimulatory factor-1 (BSF-1)/Interleukin 4 (IL 4) is a T cell product originally characterized on the basis of its actions on B lymphocytes. Recently it has been reported that BSF-1 activates T cell and mast cell lines. We now provide evidence that BSF-1, purified to homogeneity, also has a broad spectrum of activity on hematopoietic progenitor cells (HPC). However, like its action on B cells, prolierative effects were only observed when BSF-1 was combined with an additional factor. Thus BSF-1, in costimulation with recombinant G-CSF, enhances the proliferation of granulocyte-macrophage progenitor cells (CFU-GM). BSF-1 increases the proliferation of CFU-e in the presence of recombinant erythropoietin (rEPO). Furthermore, BSF-1 induces, together with rEPO, colony formation by primitive erythroid (BFU-e) and multipotent (CFU-mix) progenitor cells comparable to that observed with rEPO and interleukin 3 (IL 3). BSF-1 is also active as a megakaryocyte colony-stimulating factor; in combination with recombinant interleukin 1, rEPO or the supernatant of the T cell hybridoma FS7–20.6.18, BSF-1 induces megakaryocyte colony formation (CFU-Mk). The same factors that synergize with BSF-1 also enhance CFU-Mk proliferation induced by IL 3. Although the precise mechanisms of action of BSF-1 on HPC is not yet known, we propose that BSF-1 represents an activation factor for HPC and prepares the progenitor cells to respond to specific growth or differentiation factors.

The Ia antigens of the guinea pig have been shown to play a central role in the regulation of the immune response. We have previously partially characterized the chemical structure of these antigens. In this communication, we further characterize the structure of the five Ia antigens already described, as well as two new Ia antigens. Evidence is presented which shows that these seven Ia antigens can be organized into three distinct groups, each with a characteristic structure. The Ia.2 determinant of strain 2 and the Ia.3 and Ia.5 determinants of strain 13 animals are found on molecules composed of a 25,000 dalton chain and a 33,000 dalton chain in noncovalent association, or else are individually expressed on nonlinked 33,000 and 25,000 dalton molecules. The Ia.4 and Ia.5 determinants of strain 2 and the Ia.7 determinant of strain 13 are borne on 58,000 dalton molecules in which two chains are linked by disulfide bonds. The Ia.1 and Ia.6 determinants of strain 13 are found on a molecule of 26,000-27,000 daltons. Ia.6 of strain 2 has yet to be definitively assigned. Furthermore, in strain 13 animals the Ia.3 and Ia.5 determinants are borne on the same molecule, as are the Ia.1 and Ia.6 determinants. In strain 2 animals, the Ia.4 and Ia.5 determinants are found on the same molecule. On the basis of chemical structure, we have divided the guinea pig I region into three subregions. The accompanying paper presents evidence of associations between particular Ia genes and Ir genes.