Abstract
The linker protein LAT is expressed mainly in T and natural killer (NK) cells. LAT-deficient mice have an arrest of intrathymic T-cell development at the CD4+ CD8+ stage and lack mature T cells in the periphery. However, no gross abnormality in development and function of the B and NK cells has been described. Here we report that LAT is expressed in mouse progenitor B (pro-B) and precursor B (pre-B) cells, but not in immature or mature B cells. LAT in pre-B cells becomes tyrosine phosphorylated upon cross-linking of the pre-B-cell receptor (pre-BCR) by anti- micro antibody. Incubation of 1xN/2b (mouse pre-B-cell line) cells or bone marrow cells from microMT/ microMT mice, which lack B cells after the small pre-B-cell stage, with anti-Ig beta antibody resulted in the downregulation of LAT expression. Transgenic mice which expressed LAT protein in B-lineage cells showed an increased proportion of pro- and large pre-B cells in the bone marrow and a remarkable reduction in the numbers of mature B cells in peripheral lymphoid tissues. Collectively, the present results indicate that LAT is expressed in the cells at the early stages of B-lineage development, but is absent in immature and mature B cells. LAT may play a crucial role in the negative regulation of B-cell development at the transition from pre-B to mature B-cell stages, and signal(s) via the pre-BCR may extinguish LAT expression, thus allowing pre-B-cell differentiation towards the mature B-cell stage.