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.