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 int o recirculating cells and stops their entry into B cell follicles. Fur thermore, using radiation chimeras we demonstrate that this developmen tal 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 accumula te in the T zone and red pulp of the spleen in increased numbers, but still fail to mature to become recirculating follicular B cells. Despi te 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 recircula ting pool. Our results suggest that Syk transduces a BCR signal that i s absolutely required for the positive selection of immature B cells i nto the recirculating B cell pool.