PU.1 and Spi-B are required for normal B cell receptor-mediated signal transduction

PU.1 and Spi-B have previously been implicated in the regulation of genes encoding B cell receptor (BCR) signaling components. Spi-B(-/-) B lymphocytes respond poorly to BCR stimulation; PU.1(-/-) mice, however, lack B cells, precluding an analysis of BCR responses. We now show that PU.1(+/- )Spi-B(-/-) B cells exhibit more extensive defects than Spi-B(-/-) B cells, indicating that both PU.1 and Spi-B are required for normal BCR signaling. Strikingly, BCR cross-linking results in substantially reduced protein tyrosine phosphorylation in mutant B cells. Further analysis shows that Igα is phosphorylated and syk is recruited and becomes phosphorylated but that BLN K and PLCγ, phosphorylation are defective in mutant cells. Our data support the existence of a novel component coupling syk to downstream targets.