Surface immunoglobulins and protease inhibitors of human acute leukemia blasts

Cell‐surface proteins of human leukemic blasts were studied by direct immunofluorescence (DIF), low pH elution and immunodiffusion (ID). Among AML blasts from 21 patients, the average proportions of blasts positive for IgG, IgM, and IgA were 60%, 9%, and 9% respectively. In contrast, blasts from four CML patients in blast crisis and 14 ALL patients had surface IgG, IgM, and IgA values of 14%, 9%, and 7% respectively for the former group and 1.4%, 1.1%, and 0.8% respectively for the latter group. Blasts from 20 leukemic cell preparations were eluted at pH 2.4 for 30 min at 4° C in glycine. HC1 buffer. Immunodiffusion with appropriate specific antisera demonstrated intact IgG in 3 of 13 AML eluates. Ten of 13 AML eluates, 1 of 3 CML eluates, and 2 of 4 ALL eluates contained intact IgG and Fab fragment, but no Fc fragment. One CML eluate contained intact IgG; the remaining CML eluate contained Fab fragment only. Two ALL eluates contained no IgG or fragments by double diffusion. An eluate from a pool of normal human leukocytes from 20 normal donors contained intact IgG and Fc fragment, but no Fab fragment. Nineteen of 20 leukemic cell eluates also contained the anti‐proteases alpha‐1‐antitrypsin and alpha‐1‐anti‐chymotrypsin which were shown to have been proteolytically modified. Five of 20 leukemic cell eluates contained the anti‐protease alpha‐2‐macroglobulin. The normal leukocyte eluate contained alpha‐1‐anti‐trypsin but no alpha‐1‐anti‐chymotrypsin or alpha‐2‐macroglobulin. The presence of Fab fragment in AML, CML blast crisis and ALL eluates suggests IgG binding by Fab as antibody, while Fc fragment in normal leukocyte eluate suggests binding via Fc to the Fc receptor. The expression of cell‐associated proteolytic enzymes, as revealed by the presence of protease‐modified anti‐proteases, may explain cell‐surface IgG degradation. A consequence of surface proteolytic activity would be the degradation of IgG antibody to yield Fab fragment bound to membrane antigenic determinants. The Fab reaction product is incapable of interacting with either complement or Fc receptors. Therefore, such proteolytic activity may protect the leukemic blasts from lysis by complement‐dependent or antibody‐dependent cell‐mediated cytotoxic mechanisms.