The B lymphocyte–induced maturation protein (Blimp-1) upregulates the expression of syndecan-1 and J chain and represses that of c-myc. We have transfected Blimp-1 into two sublines of the BCL1 B cell lymphoma that represent distinct stages of B cell development in secondary lymphoid tissues. After interleukin (IL)-2 and IL-5 stimulation, the BCL1 3B3 cells differentiate into centrocyte-like cells, whereas the BCL1 5B1b cells blast and appear to be blocked at the centroblast stage. This blasting effect and the increase in IgM secretion that follows it can be blocked by a dominant negative form of Blimp-1. At the same time, the ectopic expression of Blimp-1 in these partially activated cells induces an apoptotic response that also can be suppressed by the same dominant negative protein. A similar effect was noticed when Blimp-1 was expressed in the mature L10A and the immature WEHI-231 lines, indicating this may be a general effect at earlier stages of the B cell development, and distinct from the ability of Blimp-1 to induce maturation in late stages of differentiation. Truncation mutants indicate that the induction of the apoptotic response relies mainly on 69 amino acids within Blimp-1's proline-rich domain. We propose that Blimp-1 expression defines a checkpoint beyond which fully activated B cells proceed to the plasma cell stage, whereas immature and partially activated cells are eliminated at this point.
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3 August 1998
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August 03 1998
Differential Effect of B Lymphocyte–induced Maturation Protein (Blimp-1) Expression on Cell Fate during B Cell Development
Eric J. Messika,
Eric J. Messika
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Peter S. Lu,
Peter S. Lu
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Yen-Jen Sung,
Yen-Jen Sung
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Tony Yao,
Tony Yao
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Jen-Tsan Chi,
Jen-Tsan Chi
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Yueh-hsiu Chien,
Yueh-hsiu Chien
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Mark M. Davis
Mark M. Davis
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
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Eric J. Messika
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Peter S. Lu
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Yen-Jen Sung
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Tony Yao
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Jen-Tsan Chi
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Yueh-hsiu Chien
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Mark M. Davis
From the *Howard Hughes Medical Institute, the ‡Departments of Microbiology and Immunology and §Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5428; and the ‖Department of Anatomy, National Yang-Ming University, Taipei, Taiwan 112, Republic of China
Address correspondence to Mark M. Davis, Howard Hughes Medical Institute, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5428. Phone: 650-723-7962; Fax: 650-723-7771; E-mail: [email protected]
Received:
October 07 1997
Revision Received:
May 05 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (3): 515–525.
Article history
Received:
October 07 1997
Revision Received:
May 05 1998
Citation
Eric J. Messika, Peter S. Lu, Yen-Jen Sung, Tony Yao, Jen-Tsan Chi, Yueh-hsiu Chien, Mark M. Davis; Differential Effect of B Lymphocyte–induced Maturation Protein (Blimp-1) Expression on Cell Fate during B Cell Development . J Exp Med 3 August 1998; 188 (3): 515–525. doi: https://doi.org/10.1084/jem.188.3.515
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