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Molecular and Cellular Biology, June 2005, p. 4455-4465, Vol. 25, No. 11
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.11.4455-4465.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Single and Combined Deletions of the NTAL/LAB and LAT Adaptors Minimally Affect B-Cell Development and Function

Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 9, France,¹ Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic,² Institute of Immunology, Otto von Guericke University Magdeburg, Leipzigerstrasse 44, 39120 Magdeburg, Germany³

Received 9 December 2004/ Returned for modification 13 January 2005/ Accepted 4 March 2005

NTAL (non-T-cell activation linker, also called LAB) and LAT (linker for activation of T cells) are evolutionarily related transmembrane adaptor proteins that are phosphorylated upon immunoreceptor engagement. Using quantitative reverse transcription-PCR, both NTAL and LAT were found to be expressed in B cells. However, LAT expression was limited to early B cells, whereas NTAL expression typified mature B cells. To delineate their roles in B-cell development and function, Ntal-deficient mice were generated and crossed with Lat-deficient mice. B cells developed in Lat^–/– Ntal^–/– double-deficient mice and in mice lacking either of the two adaptors with the same efficiency as in wild-type mice. Upon B-cell antigen receptor cross-linking, Ntal^–/– B cells exhibited slightly increased Ca²⁺ mobilization and proliferation. In addition, Ntal-deficient mice had increased levels of natural antibodies and slightly increased humoral response to a T-dependent antigen. Normal titers of serum-specific immunoglobulins were produced in response to a T-cell-independent antigen. Although NTAL is also expressed in plasma cells, its absence did not affect the hypergammaglobulinemia E and G1 that developed in mice with a mutation in tyrosine 136 of LAT. Therefore, NTAL does not play a role in B cells symmetric to the role played by LAT in T cells.

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