Kinetics of B cell subpopulations in peripheral lymphoid tissues: evidence for the presence of phenotypically distinct short-lived and long-lived B cell subsets.

Abstract

A small proportion of the sIg+ B lymphocytes in peripheral lymphoid organs [22% in spleen and 6% in lymph node (LN)] in rat carries the Thy-1 antigen. These Thy-1+ B cells represent newly formed bone marrow (BM) derived (or immature) B cells. In this study we investigated the kinetic behavior of Thy-1+ and Thy-1- B cells in various lymphoid tissues. The renewal rates of these B cells in young adult rats were determined by continuous administration of 5-bromo-2-deoxyuridine (BrdU) for up to 6 weeks. At several time intervals, Thy-1+ and Thy-1- B cell subpopulations in BM, blood, spleen and popliteal LN were analyzed for the presence of incorporated BrdU, using three-color immunocytology on cytospin preparations. In all tissues studied, the Thy-1+ B cells were rapidly renewed with a rate that varied between 58% (BM) and 22% (LN) per day. Virtually all Thy-1+ B cells were labeled by BrdU within a period of 8-16 days, indicating that all these cells are relatively short-lived. By contrast, the replacement of Thy-1- B cells in these tissues was 30-40 times lower, and ranged between 2.0 and 0.8% per day. In absolute numbers we estimate that 57 million Thy-1+ B cells are renewed per day in the BM whereas only 10 million Thy-1- B cells are replaced in the pool of long-lived peripheral B cells. This implicates a cell loss of 80% at the transition of the Thy-1+ to the Thy-1- B cell stage. The few B cells that actually become incorporated into the pool of mature B cells are most probably selected on the basis of the specificity of their sIg.