The Molecular Mechanism of B Cell Activation by toll-like Receptor Protein RP-105

Chan, Vivien W.F.; Mecklenbräuker, Ingrid; Su, I-hsin; Texido, Gemma; Leitges, Michael; Carsetti, Rita; Lowell, Clifford A.; Rajewsky, Klaus; Miyake, Kensuke; Tarakhovsky, Alexander

doi:10.1084/jem.188.1.93

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Article| July 01 1998

The Molecular Mechanism of B Cell Activation by toll-like Receptor Protein RP-105

Vivien W.F. Chan,

Vivien W.F. Chan

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Ingrid Mecklenbräuker,

Ingrid Mecklenbräuker

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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I-hsin Su,

I-hsin Su

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Gemma Texido,

Gemma Texido

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Michael Leitges,

Michael Leitges

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Rita Carsetti,

Rita Carsetti

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Clifford A. Lowell,

Clifford A. Lowell

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Klaus Rajewsky,

Klaus Rajewsky

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Kensuke Miyake,

Kensuke Miyake

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Alexander Tarakhovsky

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

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Author and Article Information

Vivien W.F. Chan

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Ingrid Mecklenbräuker

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

I-hsin Su

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Gemma Texido

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Michael Leitges

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Rita Carsetti

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Clifford A. Lowell

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Klaus Rajewsky

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Kensuke Miyake

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Alexander Tarakhovsky

From the *Department of Laboratory Medicine, University of California, San Francisco, California 94143; ‡Laboratory of Lymphocyte Signaling and §Department of Immunology, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany; ‖Max-Planck-Institut für Immunbiologie, Stubeweg 51, D-79108 Freiburg, Germany; and ¶Department of Immunology, Saga Medical School, Nabeshima, Saga 849, Japan

Address correspondence to Alexander Tarakhovsky, Laboratory of Lymphocyte Signaling, Institute for Genetics, University of Köln, Weyertal 121, D-50931 Köln, Germany. Phone: 49-221-470 4319; Fax: 49-221-470 4970; E-mail: [email protected]

Received: March 26 1998

Revision Received: April 17 1998

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1998

J Exp Med (1998) 188 (1): 93–101.

https://doi.org/10.1084/jem.188.1.93

The B cell–specific transmembrane protein RP-105 belongs to the family of Drosophila toll-like proteins which are likely to trigger innate immune responses in mice and man. Here we demonstrate that the Src-family protein tyrosine kinase Lyn, protein kinase C β I/II (PKCβI/II), and Erk2-specific mitogen-activated protein (MAP) kinase kinase (MEK) are essential and probably functionally connected elements of the RP-105–mediated signaling cascade in B cells. We also find that negative regulation of RP-105–mediated activation of MAP kinases by membrane immunoglobulin may account for the phenomenon of antigen receptor–mediated arrest of RP-105–mediated B cell proliferation.

1998

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