THE ROLES OF PREB CELL-RECEPTOR IN EARLY B-CELL DEVELOPMENT AND ITS SIGNAL-TRANSDUCTION

The preB cell receptor is expressed for a short period after mu heavy chain is produced, that is, at the large preB cell stage in B cell dev elopment. The severe impairment of B cell differentiation observed in mice deficient for the preB cell receptor clearly demonstrated the imp ortance of the preB cell receptor in B cell development. Analyses of b one marrow precursor B cells in normal and B cell-deficient mutant mic e indicated the preB cell receptor transduced signals to drive cell cy cle and to induce allelic exclusion. The proliferation of the preB cel l receptor-expressing cells leads to the selective expansion of cells which have succeeded in the productive rearrangement of mu heavy chain gene. This process builds up a preB cell pool large enough to generat e sufficient numbers of mature B cells. The preB cell receptor appears to induce allelic exclusion by shutting off the expression of recombi nase activation gene (RAG), In order to analyse the signal transductio n pathway downstream of the preB cell receptor, we have developed a ne w system in which cross-linking of Ig beta expressed on bone marrow pr oB cells mimics the signalling through the preB cell receptor to induc e differentiation from proB to small preB cells.