Regulation of cell morphology in B lymphocytes by IL-4: evidence for induced cytoskeletal changes.
Lymphocyte activation is often accompanied by changes in cell morphology, for example, in cell adhesion or motility. IL-4 is a cytokine exerting many effects on B lymphocytes. In this study, we show that stimulation with LPS in combination with IL-4, but not LPS or IL-4 alone, results in a pronounced dendritic morphology of B cells. Using a culture system in which Abs directed to B cell surface markers are immobilized on the tissue culture plastic, we find that cell spreading can be mediated by a variety of Abs, including anti-CD44, -CD23, -LFA-1, -VLA-4, -ICAM-1, and -Ig. B cells stimulated with anti-Ig Abs plus IL-4, or anti-CD40 Abs in the presence or absence of IL-4, are also induced to spread, while IL-2, IL-5, or IL-10 in combination with LPS or alone fail to induce this. Spreading correlates with induction of tight cell aggregation. It is sensitive to cytochalasin B, indicating a requirement for intact actin cytoskeleton. CD44 is selectively detected in the detergent-insoluble fraction of cell lysates prepared from LPS plus IL-4-stimulated B cell cultures after Ab cross-linking of CD44, suggesting a membrane protein-cytoskeleton interaction. Interestingly, electron microscopy studies reveal induction of microvilli-like structures on LPS plus IL-4-stimulated blasts, suggesting that IL-4 can influence cell morphology on an ultra-structural level. In summary, our data show that stimulation with LPS plus IL-4 or ligation of CD40 is capable of inducing dramatic morphologic changes in murine B cells, which correlates with in vitro induction of strong cell adhesion.
Davey
E J
EJ
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
Thyberg
J
J
Conrad
D H
DH
Severinson
E
E
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D019013:CD40 Antigens / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003599:Cytoskeleton / Q000187:drug effects* / Q000276:immunology; D004357:Drug Synergism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007106:Immune Sera / Q000494:pharmacology; D007075:Immunoglobulin M / Q000276:immunology; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008871:Microvilli / Q000648:ultrastructure
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D018960:Hyaluronan Receptors; D007106:Immune Sera; D007075:Immunoglobulin M; D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; C044203:anti-IgM; D016753:Interleukin-10; D015847:Interleukin-4