Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures.

Abstract

Although it has been established that IL-4 enhances both IgG1 and IgE secretion in LPS-stimulated B cell cultures, these studies failed to determine whether IL-4 preferentially induces isotype switching or preferentially allows for the maturation of precommitted precursor cells. To distinguish between these possibilities, it is necessary to ascertain the effect of IL-4 on the isotypes secreted by individual precursor cells during clonal expansion. Therefore, clonal cultures of B cells stimulated with a Th2 helper cell line specific for rabbit Ig and rabbit anti-mouse IgM were established. The majority of B cells are capable of undergoing clonal expansion under these conditions. To vary the level of IL-4 present, either IL-4 or anti-IL-4 was added to cultures. In the presence of IL-4 there was an increase in the proportion of clones that secreted IgE and a decrease in the proportion of clones that secreted IgM. The addition of IL-4 to cultures also increased the amount of IgE secreted by individual clones. Thus, these experiments definitively prove that IL-4 causes specific heavy chain class switching to IgE in Th2-stimulated B cell cultures. In contrast, IL-4 does not affect the proportion of clones secreting IgG1, suggesting that other consequences of Th cell-B cell interactions play a role in the generation of an IgG1 response.

The Transcriptional Co-activator p/CIP (NCoA-3) Is Up-regulated by STAT6 and Serves as a Positive Regulator of Transcriptional Activation by STAT6

“…IL-4 and IL-13 are considered to be crucial cytokines for the development of type II allergic diseases (4), because IL-4 can promote immunoglobulin class-switching to the IgE isotype in B cells (5), and IL-4 and IL-13 mediate the induction of Th2 differentiation (6,7). STAT6-deficient mice are defective in IL-4-and IL-13-induced Th2 cell differentiation and IL-4-induced class switching B cells to IgE and IgG1 (8 -10).…”

Inhibition of Interleukin-4-induced Class Switch Recombination by a Human Immunoglobulin Fcγ-Fcϵ Chimeric Protein

“…Because GE2 can cross-link CD32 with CD23, we tested this chimeric protein for its ability to affect IgE class switching and examined the events underlying this effect. IL-4 is a key participant in human Ig class switching and, in particular, in the production of IgE (7,8). The ␣ chain of the IL-4 receptor activates the Janus kinase (JAK) family members followed by subsequent phosphorylation and activation of STAT6 (9 -12).…”

Prediktor Asma Pada Usia 7 Tahun Setelah Menderita Bronkiolitis Akut Karena Respiratory Syncytial Virus: Suatu Studi Prospektif

“…Seperti telah diketahui bersama IL-4 merupakan sitokin utama yang mengatur produksi IgE pada asma. Peningkatan produksi IL-4 memicu peningkatan kadar IgE melalui switching sel B ke sel plasma atau sel TCD4 + berdiferensiasi menjadi sel Th2 (11)(12)(13). Dalam penelitian ini terjadi peningkatan kadar IL-4 dan rasio IL-4 / IFN-γ yang bermakna pada penderita bronkiolitis akut RSV dimasa bayi dan berkembang menjadi asma pada usia 7 tahun.…”