title: Single and combined deletions of the NTAL/LAB and LAT adaptors minimally affect B-cell development and function.
abstract: 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 Ca(2+) 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Université de la Méditerranée, Parc Scientifique de Luminy, Case 906, 13288 Marseille Cedex 9, France.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ondrej
authors.initials: O
authors.lastname: Horvath
authors.forename: Andrea
authors.initials: A
authors.lastname: Hamm-Baarke
authors.forename: Mireille
authors.initials: M
authors.lastname: Richelme
authors.forename: Claude
authors.initials: C
authors.lastname: Grégoire
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Guinamard
authors.forename: Vaclav
authors.initials: V
authors.lastname: Horejsi
authors.forename: Pavla
authors.initials: P
authors.lastname: Angelisova
authors.forename: Jiri
authors.initials: J
authors.lastname: Spicka
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Marie
authors.initials: M
authors.lastname: Malissen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation; D049109:Cell Proliferation; D017353:Gene Deletion; D015870:Gene Expression; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010950:Plasma Cells / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014443:Tyrosine / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000955:Antigens, T-Independent; C471359:LAB protein, mouse; C491734:Lat protein, mouse; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014443:Tyrosine; D002118:Calcium