Pre-B-cells in normal human bone marrow and in bone marrow from patients with leukemia in remission: persistent quantitative differences and possible expression of cell surface IgM in vitro

Pre-B-cells are bone marrow lymphoid cells that lack surface immunoglobulin (sIg-) but contain intracytoplasmic (c) IgM heavy chains and are probably the immediate precursors of immature sIgM+ B lymphocytes. To better understand early stages of B-cell development, immunofluorescence techniques were employed to identify pre-B-cells and B lymphocytes and to examine the expression of sIgM in vitro by human marrow that had been previously depleted of B cells by immunoadsorption. Marrow was derived from patients with acute leukemia in long-term remission off therapy and from a variety of controls. The pre-B-cell compartment was greatly expanded in the marrow of leukemia remission patients for more than 2 yr following cessation of therapy. A similar finding was noted in two patients with lymphoma who had also completed chemotherapy, but not in three with solid tumors prior to therapy. sIgM+ B cells appeared in cultures of sIg- marrow cells from leukemia patients, but not the controls, and only after exposure to Epstein-Barr virus (EBV). At least some of the sIgM+ lymphocytes also expressed cIgM and were probably derived from pre-B-cells. The results of this study (A) confirm that patients who have completed treatment for acute leukemia have a prolonged elevation of pre-B-cell proportions, (B) demonstrate that similar abnormalities may exist in patients with certain solid tumors following chemotherapy, and (C) suggest that a fraction of sIg- human marrow cells, perhaps pre-B-cells, bear a receptor for EBV and can be induced to express to sIgM in vitro.