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 Blood, 15 February 2006, Vol. 107, No. 4, pp. 1521-1527.
Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-05-1859.

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IMMUNOBIOLOGY

LIME acts as a transmembrane adapter mediating BCR-dependent B-cell activation

Eunseon Ahn, Hyunsook Lee, and Yungdae Yun

From the Division of Molecular Life Science, Ewha Womans University, Seoul, Korea; and Department of Biological Sciences, Seoul National University, Korea.

Assembly of a signaling complex around the transmembrane adapter LAT is essential for the transmission of T-cell receptor (TCR)-mediated signaling. However, a LAT-like molecule responsible for the initial activation events in B-cell receptor (BCR) signaling has not yet been identified. Here, we show that LIME is a transmembrane adaptor required for BCR-mediated B-cell activation. LIME was found to be expressed in mouse splenic B cells. Upon BCR cross-linking, LIME was tyrosine phosphorylated by Lyn and associated with Lyn, Grb2, PLC-{gamma}2, and PI3K. Reduction of LIME expression by the introduction of siRNA resulted in the disruption of BCR-mediated activation of MAPK, calcium flux, NF-AT, PI3K, and NF-{kappa}B. Taken together, these results establish that LIME is an essential transmembrane adaptor linking BCR ligation to the downstream signaling events that lead to B-cell activation.


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