Interleukin 4 causes isotype switching to IgE in T cell-stimulated clonal B cell cultures.
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.
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002999:Clone Cells; D005786:Gene Expression Regulation / Q000187:drug effects; D005812:Genes, Switch; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008211:Lymphocyte Cooperation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D007073:Immunoglobulin E