Interleukin‐4 induces both lgg4 and ige secretion by peripheral blood b cells

Peripheral blood mononuclear cells (PBMCs) from healthy nonallergic donors were cultured with recombinant interleukin‐4 (rIL‐4), and the Ig of different isotypes was quantitated in the culture supernatants by radioimmunoassays. Recombinant IL‐4 induced IgG4 and IgE secretion in a dose‐dependent manner, whereas it had no consistent effect on the secretion of the other isotypes. In the absence of rIL‐4, B cells in the PBMC preparations secreted <1 ng IgE/ml and a mean of 5 ng IgG4/ml. In the presence of the optimal dose of 100 U rIL‐4/ml, PBMCs from five donors secreted a mean ± SEM of 37 2 8ng IgE/ml and 66 ± 25 ng IgG4/ml. In kinetic studies, no IgG4 or IgE secretion was detected during the first 5 days of culture, and approximately 50% of the IgG4 and IgE secreted by day 15 was detected in supernatants on day 7. Cycloheximide, actinomycin‐D, and mytomycin‐C completely inhibited the rIL‐4‐induced IgG4 and IgE secretion, indicating that de novo protein, RNA, and DNA synthesis was required. As shown by Percoll buoyant density centrifugation, rIL‐4 induced B cells in the high‐density fraction to secrete IgG4 and IgE, whereas it inhibited spontaneous IgG4 secretion by low‐density B cells. Interferon‐r inhibited IL‐4‐induced lgG4 and IgE secretion. The data demonstrate that 11‐4 induces small, dense, peripheral blood B cells to secrete not only IgE but also lgG4, which paralells the IL‐4‐induced IgE and IgG1 secretion by murine B cells. Our in vitro data, the elevation of IgE and lgG4 in the serum of patients with helminth parasitic infections, and the prevalence of IgE and IgG4 antibodies to allergens suggest that the formation of these two isotypes is likely to share a common IL‐4‐dependent regulatory pathway.