SEPARATION AND REACTIVITY INVITRO OF A SUBPOPULATION OF HUMAN LYMPHOCYTES WHICH BIND HISTAMINE - CORRELATION OF HISTAMINE REACTIVITY WITH CELLULAR MATURATION

Lymphocytes reactive with histamine were fractionated on beads of Sepharose-albumin to which histamine was attached (SAH). Histamine reactive cells were present in blood, tonsil and thymus. Using membrane and functional criteria, T [thymus-derived] and B [bone marrow-derived] cells were shown to contain histamine-binding cells; precursor cells did not. In T cell populations, lectin induced proliferation, cell-mediated lymphotoxicity, and secretion of mediators (lymphocyte mitogenic factor and immunoglobulin (Ig) secretion inducing activity) were restricted to the histamine reactive lymphocyte. Antigen [tetanus toxoid] induced proliferation and mixed lymphocyte culture response mainly present in histamine-binding cells, also occurred in nonbninding populations. Reactivity with sheep erythrocytes was present in reactive and non-reactive cells. In B cell populations, reactivity with antisera of IgM occurred in binding and non-binding cells, while reactivity with antisera to IgG as well as T cell-induced IgG secretion were confined to histamine-binding cells. Membrane reactivity to erythrocyte coated with the first 4 components of complement was characteristic of histamine-unreactive cells. In T and B populations, histamine unreactive cells responded to lymphocyte mitogenic factor. These facts, plus data from long-term lymphoid lines showing differentiation from non-binding to binding cells after cell division, lead to the concept that generation of detectable histamine sites was a differentiative lymphocyte process. The generation of histamine-binding cells in precursor cell cultures supports this hypothesis. A possible role of histamine as a physiological lymphocyte regulating agent is suggested by the inhibition by soluble histamine of proliferative, cytotoxic and secretory responses of histamine-binding T cells.