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The Journal of Immunology, 2004, 172: 6810-6819.
Copyright © 2004 by The American Association of Immunologists

Linker for Activation of B Cells: A Functional Equivalent of a Mutant Linker for Activation of T Cells Deficient in Phospholipase C-{gamma}1 Binding1

Erin Janssen, Minghua Zhu, Brandon Craven and Weiguo Zhang2

Department of Immunology, Duke University Medical Center, Durham, NC 27710

Adaptor proteins have important functions in coupling stimulation through immunoreceptors with downstream events. The adaptor linker for activation of B cells (LAB)/non-T cell activation linker (NTAL) is expressed in various immune cell types and has a similar domain structure as linker for activation of T cells (LAT). In this study we generated a LAB transgenic mouse to compare the functional differences between LAB and LAT. A LAB transgene expressed in LAT-deficient T cells was able to restore T cell development. However, these mice developed severe organomegaly with disorganized lymphoid tissues. Lymphocytes from these transgenic mice were hyperactivated, and T cells produced large amounts of type II cytokines. In addition, these activities appeared to be uncoupled from the TCR. An examination of the signaling capabilities of these T cells revealed that LAB resembled a LAT molecule unable to bind phospholipase C-{gamma}1.




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