B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals

Only mature B lymphocytes can enter the lymphoid follicles of spleen and ly mph nodes and thus efficiently participate in the immune response. Mature, long-lived B lymphocytes derive from short-lived precursors generated in th e bone marrow. We show that selection into the mature pool is an active pro cess and takes place in the spleen. Two populations of splenic B cells were identified as precursors for mature B cells. Transitional B cells of type 1 (T1) are re cent immigrants from the bone marrow. They develop into the t ransitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen. Mature B cells can be generated fr om T1 or T2 B cells. Mice with genetic deletions of elements participating in the B cell recepto r signaling cascade display developmental arrest at the T1 or T2 stage. The analysis of these defects showed that the development of T2 and mature B c ells from T1 precursors requires defined qualitative and quantitative signa ls derived from the B cell receptor and that the induction of longevity and maturation requires different signals.