Disruption of the Bcl6 Gene Results in an Impaired Germinal Center Formation

Fukuda, Tetsuya; Yoshida, Takehiko; Okada, Seiji; Hatano, Masahiko; Miki, Tohru; Ishibashi, Kazuki; Okabe, Shinichiro; Koseki, Haruhiko; Hirosawa, Shinsaku; Taniguchi, Masaru; Miyasaka, Nobuyuki; Tokuhisa, Takeshi

doi:10.1084/jem.186.3.439

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Article| August 04 1997

Disruption of the Bcl6 Gene Results in an Impaired Germinal Center Formation

Tetsuya Fukuda,

Tetsuya Fukuda

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Takehiko Yoshida,

Takehiko Yoshida

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Seiji Okada,

Seiji Okada

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Masahiko Hatano,

Masahiko Hatano

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Tohru Miki,

Tohru Miki

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Kazuki Ishibashi,

Kazuki Ishibashi

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Shinichiro Okabe,

Shinichiro Okabe

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Haruhiko Koseki,

Haruhiko Koseki

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Shinsaku Hirosawa,

Shinsaku Hirosawa

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Masaru Taniguchi,

Masaru Taniguchi

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Nobuyuki Miyasaka,

Nobuyuki Miyasaka

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Takeshi Tokuhisa

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

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Author and Article Information

Tetsuya Fukuda, Takehiko Yoshida, Seiji Okada, Masahiko Hatano, Tohru Miki, Kazuki Ishibashi, Shinichiro Okabe, Haruhiko Koseki, Shinsaku Hirosawa, Masaru Taniguchi, Nobuyuki Miyasaka, Takeshi Tokuhisa

From the *Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the ‡First Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo 113, Japan; and the §Core Research for Evolutional Science and Technology, Division of Molecular Immunology, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan

Address correspondence to Takeshi Tokuhisa, Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan. Phone: 81-43-226-2181; FAX: 81-43-226-2183; E-mail: [email protected]

1

Abbreviations used in this paper: AFC, antibody-forming cell; AP, alkaline phosphatase; Bcl6^−/−, Bcl6-deficient mice; Bcl6^−/−RM, RAG1-deficient mice reconstituted with bone marrow cells from Bcl6-deficient mice; BM, bone marrow; BrdU, 5-bromo-2′-deoxyuridine; CD40L, CD40 ligand; CG, chicken γ globulin; GC, germinal center; GST, glutathione-S-transferase; HRP, horseradish peroxidase; NP, 4-hydroxy-3-nitrophenyl acetyl; PALS, periarteriolar lymphoid sheath; PNA, peanut agglutinin; RAG1^−/−, RAG1-deficient mice; sIg, surface Ig.

Received: April 24 1997

Revision Received: May 23 1997

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1997

J Exp Med (1997) 186 (3): 439–448.

https://doi.org/10.1084/jem.186.3.439

The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B cell lymphomas, and its products are expressed highly in germinal center (GC) B cells. To investigate the function of Bcl6 in lymphocytes, we have generated RAG1-deficient mice reconstituted with bone marrow cells from Bcl6-deficient mice (Bcl6^−/−RM). Lymphogenesis in primary lymphoid tissues of Bcl6^−/−RM is normal, and Bcl6^−/−RM produced control levels of primary IgG1 antibodies specific to T cell–dependent antigens. However, GCs were not found in these mice. This defect was mainly due to the abnormalities of B cells. Therefore, Bcl6 is essential for the differentiation of GC B cells.

1997

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