Cutting edge: the development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor alpha, and Th2 cells.
Although IL-4-producing B cells (B effector 2 cells) are found following infection and immunization, the signals regulating IL-4 production by Be2 cells are unknown. We show that culturing naive B cells with Th2 cells induces up-regulation of IL-4 in the B cells with a concomitant down-regulation of T-bet, IL-12Rbeta2, and IFN-gamma. Up-regulation of IL-4 in the Be2 cells is dependent on both T cells and IL-4 as IL-4Ralpha-deficient B cells primed with Th2 cells did not transcribe IL-4, and B cells primed in the presence of IL-4-deficient Th2 cells produced IFN-gamma instead of IL-4. Likewise, the in vivo development of IL-4-expressing B cells in a nematode infection model was dependent on both T cells and IL-4Ralpha-mediated signals. Thus, the differentiation of naive B cells into IL-4-expressing Be2 cells is regulated by a combination of T cell-dependent signals and the cytokine environment and this process is critically dependent upon the IL-4/IL-4R signaling pathway.
Harris
David P
DP
Trudeau Institute, Saranac Lake, NY 12983, USA.
Goodrich
Stephen
S
Mohrs
Katja
K
Mohrs
Markus
M
Lund
Frances E
FE
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D009351:Nematospiroides dubius / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology; D053707:Receptors, Interleukin-12; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology*; D053662:Interleukin-4 Receptor alpha Subunit
D007371:Interferon-gamma; D015847:Interleukin-4; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit