Deletion of the LIME adaptor protein minimally affects T and B cell development and function.
LIME (Lck-interacting membrane protein) is a transmembrane adaptor that associates with the Lck and Fyn protein tyrosine kinases and with the C-terminal Src kinase (Csk). To delineate the role of LIME in vivo, LIME-deficient mice were generated. Although Lime transcripts were expressed in immature and mature B and T cells, the absence of LIME impeded neither the development nor the function of B and T cells. TCR transgenic mice deprived of LIME showed, however, a 1.8-fold enhancement in positive selection. Since B cells and activated T cells express LIME and the related adaptor NTAL, mice lacking both adaptors were generated. Double-deficient mice showed no defect in the development and function of B and T cells, and the lack of LIME had no effect on the autoimmune syndrome that develops in aged NTAL-deficient mice. In contrast to a previous report, we further showed that this autoimmune syndrome develops in the absence of T cells. Therefore, our in vivo results refute all the previous roles postulated for LIME on the basis of studies of transformed B and T cells and demonstrate that LIME has no seminal role in the signaling cassette operated by antigen receptors and coreceptors.
Grégoire
Claude
C
Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France.
Simova
Sarka
S
Wang
Ying
Y
Sansoni
Amandine
A
Richelme
Sylvie
S
Schmidt-Giese
Anja
A
Simeoni
Luca
L
Angelisova
Pavla
P
Reinhold
Dirk
D
Schraven
Burkhart
B
Horejsi
Vaclav
V
Malissen
Bernard
B
Malissen
Marie
M
D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D033942:Adaptor Proteins, Vesicular Transport; C480489:Lck-interacting protein, mouse