Interleukin‐3‐treated non‐B, non‐T cells switch activated B cells to IgG₁/IgE synthesis

Abstract

The switch of activated B cells to IgE synthesis is an interleukin (IL)-3-dependent process. It is currently thought that specific T cells activated by antigen presented in the context of class II major histocompatibility complex are the major source of IL-4. Recently it has been demonstrated that a splenic non-T non-B cell population (termed NBNT) has the capacity to produce IL-4 following IgE and IgG receptor cross-linkage. In this study we demonstrate that IL-4 producing NBNT cells can induce the switch of lipopolysaccharide-activated B cells to the synthesis of IgG1 and IgE antibodies. Furthermore, it was found that not only IgE receptor cross-linkage but IL-3 was able to stimulate NBNT cells to produce IL-4 and induce the switch of B cells to IgE synthesis. NBNT cells derived from the spleen and bone marrow of SCID mice were able to produce IL-4 on exposure to IL-3. This suggested that the ability of IL-3 to stimulate IL-4 production was not dependent on prior exposure of the NBNT cells to antibody complexes in vivo. Taken together these findings represent the first observation that enough IL-4 is produced by NBNT cells to actually influence a B cell IgG/Ig response. The findings also clearly demonstrate that B cells do not need high concentrations of IL-4 to be directed to switch to IgG1 and IgE synthesis.

IL‐4: a key cytokine in atopy

“…Human bone marrow non-B-, non-T-cells, belonging to mast cells and/or basophil lineages, when activated by anti-IgE antibodies could express mRNA for, and produce, IL-4 [53]. Fc-e-receptor* cells were the major source of antigen-induced IL-4 in spleen of mice infected with Schi,stosoma mansoni [54], IL-3 treated non-B-, non-T-cells switched activated B-cells to IgGl/ IgE synthesis in mice [55].…”

The development of IgE+ memory B cells following primary IgE immune responses

“…4), indicating that no IgE' memory suggests that no memory €3 cells were induced during the course of the p r h a r y immunization or infections. However, the N. brusiliensis-infected mice were capable of Serum was collected at days 5, 7, and 11 Mice receiving a third BPO-KLWalum immunization also mounted large and rapid IgE responses, increasing after 12 days from 32 to 52 Fg/ml (Fig. 5B).…”

Exogenous Interleukin–3 Enhances IL–4 Production by Splenic CD4+ Cells during the Early Stages of a Trichinella spiralis Infection

“…It has been reported that IL–3 stimulates non–B non–T cells to produce IL–4 [] ]which then induce the switch of B cells to IgG1/IgE synthesis [25]. Recently, it has been shown that splenic non–B non–T cell from sperm whale myoglobin (SwMb)–immunized Schistosoma mansoni–infected mice do not respond directly to SwMb, but produce IL–4 in response to IL–3 [26].…”