Severe B cell deficiency in mice lacking the Tec kinase family members Tecand Btk

The cytoplasmic protein tyrosine kinase Tec has been proposed to have impor tant functions in hematopoiesis and lymphocyte signal transduction. Here we show that Tec-deficient mice developed normally and had no major phenotypi c alterations of the immune system. To reveal potential compensatory roles of other Tec kinases such as Bruton's tyrosine kinase (Btk), Tec/Btk double -deficient mice were generated. These mice exhibited a block at the B220(+) CD43(+) stage of B cell development and displayed a severe reduction of per ipheral B cell numbers, particularly immunoglobulin (Ig)M(Io)IgD(hi) B cell s. Although Tec/Btk(null) mice were able to form germinal centers, the resp onse to T cell-dependent antigens was impaired. Thus, Tec and Btk together have an important role both during B cell development and in the generation and/or function of the peripheral B cell pool. The ability of Tec to compe nsate for Btk may also explain phenotypic differences in X-linked immunodef iciency (xid) mice compared with human X-linked agammaglobulinemia (XLA) pa tients.