title: TAK1 maintains the survival of immunoglobulin λ-chain-positive B cells.
abstract: TAK1 (MAP3K7) mediation of the IκB kinase (IKK) complex-nuclear factor-κB (NF-κB) pathway is crucial for the activation of immune response and to perpetuate inflammation. Although progress has been made to understand TAK1 function in the B-cell receptor (BCR) signaling, the physiological roles of TAK1 in B-cell development, particularly in the bone marrow (BM), remain elusive. Previous studies suggested that the IKK complex is required for the development of immunoglobulin light chain λ-positive B cells, but not for receptor editing. In contrast, NF-κB activity is suggested to be involved in the regulation of receptor editing. Thus, NF-κB signaling in early B-cell development is yet to be fully characterized. Therefore, we addressed the role of TAK1 in early B-cell development. TAK1-deficient mice showed significant reduction of BM Igλ-positive B-cell numbers without any alteration in the BCR editing. Furthermore, the expression of survival factor Bcl-2 was reduced in TAK1-deficient BM B cells as assessed by microarray and quantitative PCR analyses. Ex vivo over-expression of exogenous Bcl-2 enhanced the survival of TAK1-deficient Igλ-positive B cells. TAK1-IKK-NF-κB signaling contributes to the survival of λ-chain-positive B cells through NF-κB-dependent anti-apoptotic Bcl-2 expression.
authors.affiliation: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.
authors.forename: Hisaaki
authors.identifier: http://orcid.org/0000-0002-6331-2138
authors.initials: H
authors.lastname: Shinohara
authors.affiliation: Division of Cell Proliferation, ART, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagashima
authors.affiliation: Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.|Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Marilia I
authors.initials: MI
authors.lastname: Cascalho
authors.affiliation: Laboratory for Lymphocyte Differentiation, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan.|Laboratory for Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka, 565-0871, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology*; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression; D019254:Genes, bcl-2; D007146:Immunoglobulin lambda-Chains / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D007146:Immunoglobulin lambda-Chains; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D000099151:MAP Kinase Kinase Kinase 7