The injection of bacterial lipopolysaccharide (LPS) 1 in mice causes the release of biological mediators into the serum. High concentrations of factors with various biological effects are found in the serum of mice that were treated with Bacille bili~ de Calmette-Gu~rin (BCG) or Corynebacterium parvum before injection with LPS. Serum of mice so-treated is called tumor necrosis serum (TNS), because it causes acute partial necrosis and subsequent regression of syngeneic tumor transplants in mice (1). In addition to the anti-tumor effect, TNS influences immunological functions: it contains factors that replace helper T cells in the humoral immune response (2) and that induce phenotypic and functional differentiation of B lymphocytes (3).In this report, we investigate the effect of TNS on the generation of cytotoxic cells in vitro. We show that two serologically distinct types of cytotoxic cells are generated in murine spleen-cell cultures in the absence of specific stimulus. One type arises in the presence of TNS and expresses the cell-surface antigen, Qa5, which is controlled by the Q region of chromosome 17 (4). This cell does not express the T-cell surface marker Thy-1, in contrast to a second type that arises spontaneously in tissue culture. We refer to both types of nonspecific cytotoxic cells as natural killer (NK) cells.NK cells appear in murine spleens at ~3 wk of age and become undetectable ~3 mo later (5, 6). Serological studies indicate the expression of Thy-1 (7), , and NK (9) cell-surface antigens on NK-cell populations. A number of reagents increase NK activity in young animals and induce reoccurrence of NK cells in older animals.Among these reagents are LPS (10), BCG (11), and C. parvum (12); substances that are prerequisites for the release of biologically active mediators in TNS (1).
To study affinity differences in precursors of anti-hapten antibody-forming cells, an anti-hapten response was induced in mouse spleen cell cultures. The response was measured as specific high and low affinity plaque-forming cells. Selective inhibition of high affinity response was achieved both by free hapten, and by removal of high affinity precursor cells as rosette-forming cells.The data suggest a clonal predetermination of specific precursor cells to different affinity classes.
Mice of various strains were immunized with pneumococcal polysaccharide type 14 (pneumo-14), and their anti-pneumo-14 antibodies were measured by the Farr test. Mice of strains BALB/c, ST/b, NZB and CBA (Ig allotypes a, e or j) had 300-1700 ng of antibody nitrogen per millilitre of serum on day 7. The corresponding values for C57BL/Ka, RF or AKR mice (allotypes b, c or d) were 40-300 ng/ml. Two families of congenic strains were tested, one with the C57BL and the other with the BALB/c background genome. Their response was either high or low depending on the VH genes, and other gene loci had little effect on the concentration of anti-pneumo-14 antibodies.
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