STAT6 is required for the regulation of IL-4-induced cytoskeletal events in B cells.
During lymphocyte activation, changes in cell morphology are commonly observed. This reflects cell functions important for the regulation of immune responses such as cell adhesion or cell migration. Notably, IL-4 has been shown to induce adhesion and locomotion in B cells, and we have recently described that IL-4 causes dramatic changes in B cell morphology. Thus, such B cells spread with dendritic cell protrusions and produce microvilli-like structures. The molecular mechanisms by which IL-4 induces these complex changes are currently unknown. Two signal transduction pathways are well described for IL-4, i.e. one involving insulin receptor substrate (IRS)-2 and a Janus kinase (JAK)/ signal transducer and activator of transcription (STAT) pathway mediated by STAT6. In this study we therefore used B cells from STAT6-deficient mice to address the question of a possible STAT6 dependence in IL-4-induced morphology changes. By light and electron microscopy, cell spreading and polarization were found to be severely impaired and microvilli formation was reduced. In contrast, only mild impairment was observed in cell adhesion in B cells from STAT6-deficient mice. Our results show that adhesion can be induced in the absence of STAT6. However, expression of STAT6 is necessary for optimal responses in both cell adhesion and microvilli induction. STAT6 is also essential to allow an IL-4-dependent spreading or polarization response. A possible interpretation of our results is that STAT6-dependent expression of a specific gene or genes is required for IL-4 to affect changes in B cell morphology.
Davey
E J
EJ
Department of Cell and Molecular Biology, Box 285, Karolinska Institutet, 171 77 Stockholm, Sweden.
Greicius
G
G
Thyberg
J
J
Severinson
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D055504:Insulin Receptor Substrate Proteins; D015847:Interleukin-4 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010750:Phosphoproteins / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000032:analysis; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*
D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526298:Irs2 protein, mouse; D008070:Lipopolysaccharides; D010750:Phosphoproteins; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4; D004247:DNA