The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/439/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 3, August 4, 1997 439-448

Articles

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

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

From the * Division of Developmental Genetics, Center for Biomedical Science, Chiba University School of Medicine, Chiba 260, Japan; the {ddagger} 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

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.

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: tokuhisa{at}med.m.chiba-u.ac.jp

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 {gamma} 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.


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