The Journal of Experimental Medicine
Janeway's Immunobiology 7th Edition
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Published online 27 November 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1577/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1577-1586

Original Article

Migration and Differentiation of Autoreactive B-1 Cells Induced by Activated {gamma}/{delta} T Cells in Antierythrocyte Immunoglobulin Transgenic Mice

Norihiko Watanabea,b, Koichi Ikutaa, Sidonia Fagarasana, Shujiro Yazumib, Tsutomu Chibab, and Tasuku Honjoa
a Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
b Department of Gastroenterology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

Correspondence to: Tasuku Honjo, Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan. Tel:81-75-753-4371 Fax:81-75-753-4388 E-mail:honjo{at}mfour.med.kyoto-u.ac.jp.

Using normal and transgenic (Tg) mice, we have shown that peritoneal B-1 cells are activated by administration of cytokines or lipopolysaccharide and migrate to other lymphoid organs where they differentiate into antibody-secreting cells. However, little is known about the process of B-1 cell migration and differentiation in vivo. We developed a mouse line by crossing the antierythrocyte antibody Tg mice (HL mice) with TCR-{gamma}/{delta} Tg mice specific for a self-thymus leukemia (TL) antigen in the recombination activating gene (RAG)2-/- background. In the presence of the self-antigen, Tg {gamma}/{delta} T cells increased in number and manifested activated phenotypes. Peritoneal B-1 cells in these mice migrated into mesenteric lymph nodes and differentiated into autoantibody-secreting cells, resulting in strong autoimmune hemolytic anemia. Furthermore, transfer of RAG2-/- x HL bone marrow or peritoneal cells into the peritoneal cavity of RAG2-/- x TCR-{gamma}/{delta} Tg mice gave rise to donor-derived B-1 cells in mesenteric lymph nodes, and these cells produced the autoantibody. Thus, this study demonstrates that the migration of B-1 cells and differentiation into the antibody-secreting cells can be induced by noncognate T cell help and implies the possibility that {gamma}/{delta} T cells may induce B-1 cell differentiation in vivo.

Key Words: RAG2 deficient, {gamma}/{delta} TCR transgenic, germinal center, peritoneal cavity, hemolytic anemia


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