Phenotypes of ''Null'' Lymphoid Cells in Human Blood

F(ab')2 antibody fragments of heteroantisera directed against p28,33 (or 'Ia-like') antigen, T-cell antigen(s) (T), myeloid antigen (M), and immunoglobulin have been used along with rosetting techniques to analyse the antigenic heterogeneity of 'null' or 'unclassified' lymphoid cells purified 'negatively' from human blood by E rosette depletion of T cells and B removal on an anti-immunoglobulin immunoabsorbent. The results confirm that considerable heterogeneity exists within the 'null' cell population; the majority of cells are p28,33+ and Fcgamma-receptor-positive, and a proportion but not all of these p28,33+, Fcgamma+ cells are also C3-receptor-positive but negative for the other heteroantigens (T and M). 2-6% were 'pre-B' by the criteria of immunofluorescent staining for cytoplasmic IgM in the absence of detectable cell surface Ig. 1-3% stained intensely with anti-IgM, anti-IgG or anti-IgA, or anti-k plus anti-lambda and were presumed to be plasma cells or their immediate precursors. No null cells stained with antibody to terminal deoxynucleotidyl transferase enzyme, a marker for early T lineage cells, and less than 1% expressed an acute ('non-T, non-B') lymphoblastic-leukaemia-associated membrane antigen which is believed to be an 'early' lymphoid lineage differentiation marker. A minor subpopulation made sheep 'E' rosettes, and another made mouse 'E' rosettes after neuraminidase pretreatment of the lymphoid cells. A small proportion of 'lymphoid', 'null cells' were reactive with an anti-myelomonocytic (M) antibody. It is suggested that 'null' lymphoid cells in blood are heterogeneous and that most are not immature T or B precursors but either a relatively mature B lymphocyte population with a very low density of membrane immunoglobulin or a distinct non-T, non-B cell type.