Lewis L. Lanier

A Map of the Cell Surface Antigens Expressed on Resting and Activated Human Natural Killer Cells

The major categories of human peripheral blood leukocytes were initially defined by morphology. Three classifications were identifiable: granulocytes, monocytes, and lymphocytes. Within the lymphocyte group, the cells were considered homogeneous and undistinguished, displaying a small roundish nucleus and scant cytoplasm. The vast heterogeneity within the lymphoid population was not appreciated until relatively recently, when it was shown that the presence or absence of certain cell surface antigens could be correlated with cellular lineage and function. The initial subdivision of lymphocytes was based largely on two properties. Expression of surface and/or cytoplasmic immunoglobulin became the standard criterion for the B lymphocytes. Since expression of immunoglobulin is exclusively a product of B lymphocytes and strictly relates to the function of antigen binding and triggering, it still is the most definitive marker for these cells. The presence of a cell surface receptor for binding sheep erythrocytes (E) was considered the benchmark for the human T cell population (1). However, as we discuss below, this receptor can be detected on cells not of thymic origin. With the recent discovery of the T cell-associated receptor for antigen, cytoplasmic or surface expression of the T cell antigen receptor will likely replace the E receptor as the ultimate indicator of the T lymphocyte lineage (2,3).

Triggering Structures on NK Cells

Natural killer (NK) cells are a subpopulation of lymphocytes distinct from both T and B cells (Lanier et al., 1986d). In man, NK cells are identified as lymphocytes with the antigenic phenotype membrane CD3e −, CD16+ and/or CD56+ (Lanier et al., 1986d). In the mouse, NK cells are membrane CD3e −, and in some strains NK1.1+. Unlike T lymphocytes, NK cells do not rearrange T-cell receptor (TCR) α, β, γ, or δ genes (Lanier et al., 1986a, 1986b; Tutt et al., 1986, 1987; Loh et al., 1988). NK cell function and maturation, moreover, is normal in scid mice (Hackett et al., 1986; Tutt et al., 1987), in which the development of T and B lymphocytes is arrested due to a defect in the process necessary for rearrangement of immunoglobulin and T-cell antigen receptor (Bosma et al., 1983; Schuler et al., 1986; Bosma et al., 1991). These observations suggest that NK cells constitute a distinct lineage of lymphocytes, and they indicate that the recombinase mechanisms present in B and T lymphocytes are not required for NK development or function. A relationship between T and NK progenitor cells prior to TCR rearrangement is nonetheless quite possible, given the remarkable similarities in the functional and antigenic phenotypes of these lymphocytes.