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© The Rockefeller University Press, 0022-1007/1997/12/2013/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 12, December 15, 1997 2013-2021

Article

Syk Tyrosine Kinase Is Required for the Positive Selection of Immature B Cells into the Recirculating B Cell Pool

Martin Turner*, Adam Gulbranson-Judge{ddagger}, Marian E. Quinn*, Alice E. Walters*, Ian C.M. MacLennan{ddagger}, and Victor L.J. Tybulewicz*

From the * National Institute for Medical Research, Mill Hill, London, NW7 1AA, United Kingdom; and the {ddagger} Department of Immunology, University of Birmingham Medical School, Birmingham, B15 2TT, United Kingdom

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.

Address correspondence to V.L.J. Tybulewicz, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK. Phone: 44-181-913-8699; FAX: 44-181-906-4477; E-mail: v-tybule @nimr.mrc.ac.uk

The work in London was supported by the Medical Research Council and the work in Birmingham was supported by a Medical Research Council program grant.

1 Abbreviations used in this paper: BCR, B cell antigen receptor; BLR1, Burkitt's lymphoma receptor 1; BrdU, 5'-bromo-2-deoxyuridine; ITAM, Immune receptor tyrosine-based activation motif.


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