title: I-kappa B kinase beta is critical for B cell proliferation and antibody response.
abstract: The NF-kappaB proteins are critical in the regulation of the immune and inflammatory response. Stimulation of the NF-kappaB pathway leads to increases in I-kappaB kinase beta (IKKbeta) kinase activity to result in the enhanced phosphorylation and degradation of I-kappaB and the translocation of the NF-kappaB proteins from the cytoplasm to the nucleus. In this study, a dominant-negative IKKbeta mutant expressed from the IgH promoter was used to generate transgenic mice to address the role of IKKbeta on B cell function. Although these transgenic mice were defective in activating the NF-kappaB pathway in B cells, they exhibited no defects in B lymphocyte development or basal Ig levels. However, they exhibited defects in the cell cycle progression and proliferation of B cells in response to treatment with LPS, anti-CD40, and anti-IgM. Furthermore, selective defects in the production of specific Ig subclasses in response to both T-dependent and T-independent Ags were noted. These results suggest that IKKbeta is critical for the proliferation of B cells and the control of some aspects of the humoral response.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Aurelia
authors.initials: A
authors.lastname: Schmalstieg
authors.forename: Dorothy
authors.initials: D
authors.lastname: Yuan
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gaynor
mesh_terms: D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D051550:I-kappa B Kinase; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000955:Antigens, T-Independent; D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D006241:Haptens; D007136:Immunoglobulins; D016328:NF-kappa B; C054401:trinitrophenyl keyhole limpet hemocyanin; D006433:Hemocyanins; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse