title: Unexpected requirement for ZAP-70 in pre-B cell development and allelic exclusion.
abstract: ZAP-70, a member of the Syk family of tyrosine kinases, has been reported to be expressed exclusively in T and NK cells. We show here that it is expressed throughout B cell development and that it plays a role in the transition of pro-B to pre-B cells in the bone marrow, a checkpoint controlled by signals from the pre-B cell receptor (pre-BCR), which monitors for successful rearrangement of immunoglobulin heavy chain genes. Whereas mice deficient in Syk show a partial block at this step, mice mutant in both Syk and ZAP-70 show a complete block at the pro-B cell stage and a failure of heavy chain allelic exclusion, hallmarks of defective pre-BCR signaling.
authors.affiliation: National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
authors.forename: Edina
authors.initials: E
authors.lastname: Schweighoffer
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: Anne
authors.initials: A
authors.lastname: Mathiot
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D004792:Enzyme Precursors / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D038041:Lymphopoiesis; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell; D000072377:Syk Kinase; D051746:ZAP-70 Protein-Tyrosine Kinase
chemical_list: D004792:Enzyme Precursors; D007143:Immunoglobulin Heavy Chains; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse