Unexpected requirement for ZAP-70 in pre-B cell development and allelic exclusion.
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.
Schweighoffer
Edina
E
National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Vanes
Lesley
L
Mathiot
Anne
A
Nakamura
Tetsuya
T
Tybulewicz
Victor L J
VL
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
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