title: Redundant role for Zap70 in B cell development and activation.
abstract: Expression of the Syk family tyrosine kinase Zap70 is strongly correlated with poor clinical outcome in chronic lymphocytic leukemia, the most common human leukemia characterized by B cell accumulation. The expression of Zap70 may reflect the specific cell of origin of the tumor or may contribute to pathology. Thus, the normal role of Zap70 in B cell physiology is of great interest. While initial studies reported that Zap70 expression in the mouse was limited to T and NK cells, more recent work has shown expression in early B cell progenitors and in splenic B cells, suggesting that the kinase may play a role in the development or activation of B cells. In this study, we show that Zap70 is expressed in all developing subsets of B cells as well as in recirculating B cells, marginal zone B cells and peritoneal B1 cells. Analysis of Zap70-deficient mice shows no unique role for Zap70 in either the development of B cells or in their in vitro and in vivo activation. However, we show that Zap70 can rescue the defective positive selection of immature B cells into the recirculating pool in Syk-deficient mice, demonstrating functional redundancy between these two kinases.
authors.affiliation: Division of Immune Cell Biology, MRC National Institute for Medical Research, London, UK.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Fallah-Arani
authors.forename: Edina
authors.initials: E
authors.lastname: Schweighoffer
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000072377:Syk Kinase; D014611:Vaccination; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D006241:Haptens; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; C054401:trinitrophenyl keyhole limpet hemocyanin; D006433:Hemocyanins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse