The persisting (P) cell: Histamine c cell-derived factor, origin from a b, and relationship to mast cells (P-cell stimulating factor/T-cell hybridoma/T-cell growth factor/mu

Histamine was detected at levels of 100 ng/106 cells in the metachromatic granules of the persisting (P) cell, which appears in cultures of murine lymphoid or bone marrow cells and is capable of long-term growth in vitro in the presence of a T cell- derived growth factor. This factor, which we termed P-cell stimu- lating factor, was distinct from T-cell growth factor and had an ap- parent molecular weight of 25,000-30,000. P cells did not origi- nate from Thy. I-positive cells nor was the thymus necessary for the development of their precursors. Moreover, P cells grew di- rectly from colonies generated in agar cultures of bone marrow cells, the nature of the colonies indicating that P cells shared a com- mon precursor with hemopoietic cells. Mutant Wf/Ws mice, al- though deficient in certain mast cells, possessed P-cell precursors. It is hypothesized that P cells are related to a specialized subset of mast cells, derived from a bone marrow progenitor but regulated by activated T cells. Two classes of cells are characterized by metachromatically staining cytoplasmic granules containing, among other sub- stances, histamine. These cells, mast cells and basophils, act as effector cells in antibody-mediated (1) and T cell-mediated (2) hypersensitivity reactions. Burnet has suggested that at least some mast cells are postmitotic derivatives of T lymphocytes (3, 4), basing this proposal on his observation of the large numbers of mast cells in the thymus of certain mice (4) and, subsequently, upon observations including the growth of mast cells in tissue cultures of thymus cells (5, 6) and the failure of congenitally athymic (nu/nu) mice to respond to intestinal parasites with a local mastocytosis (7). Furthermore, it has been claimed that T cells are the precursors of the mast cells in the gut mucosa (8). Here we demonstrate that cells that are capable of prolonged clonal growth in vitro in the presence of a T cell-derived factor and which we have termed persisting (P) cells (9, 10) contain histamine localized in large granules that resemble those of mast cells. These mast cell-like cells are generated from a bone mar- row-derived progenitor common to other hemopoietic cells and not from T cells, but are regulated by a T cell-derived factor.