PROLACTIN IMMUNOGLOBULIN-G COMPLEXES FROM HUMAN SERUM ACT AS COSTIMULATORY LIGANDS CAUSING PROLIFERATION OF MALIGNANT B-LYMPHOCYTES

Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-pr olactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of pro lactin with IgG was purified from serum by anti-human prolactin affini ty chromatography and was shown to contain close to 1 mole of N-epsilo n-(gamma-glutamyl)lysine crosslinks per mole of complex, a characteris tic feature in structures crosslinked by transglutaminase. Interesting ly, the complex caused a proliferation of cells from a subset of patie nts with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimul ated the proliferation of cells in the bioassay but had no effect on t he complex-responsive cells from the patients. Competition studies wit h prolactin and free Fc fragment of IgG demonstrated a necessity for e ngaging both the prolactin and the immunoglobulin receptors for prolif eration. More importantly, competition for the growth response by free prolactin and IgG suggests both possible reasons for the slow growth of this neoplasm as well as avenues for control of the disease.