Syk tyrosine kinase is required for the positive selection of immature B cells into the recirculating B cell pool.
The tyrosine kinase Syk has been implicated as a key signal transducer from the B cell antigen receptor (BCR). We show here that mutation of the Syk gene completely blocks the maturation of immature B cells into recirculating cells and stops their entry into B cell follicles. Furthermore, using radiation chimeras we demonstrate that this developmental block is due to the absence of Syk in the B cells themselves. Syk-deficient B cells are shown to have the life span of normal immature B cells. If this is extended by over-expression of Bcl-2, they accumulate in the T zone and red pulp of the spleen in increased numbers, but still fail to mature to become recirculating follicular B cells. Despite this defect in maturation, Syk-deficient B cells were seen to give rise to switched as well as nonswitched splenic plasma cells. Normally only a proportion of immature B cells is recruited into the recirculating pool. Our results suggest that Syk transduces a BCR signal that is absolutely required for the positive selection of immature B cells into the recirculating B cell pool.
Turner
M
M
National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom.
Gulbranson-Judge
A
A
Quinn
M E
ME
Walters
A E
AE
MacLennan
I C
IC
Tybulewicz
V L
VL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002469:Cell Separation; D004792:Enzyme Precursors / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D000072377:Syk Kinase
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse