Prolactin-immunoglobulin G complexes from human serum act as costimulatory ligands causing proliferation of malignant B lymphocytes

Ameae M. Walker, David W. Montgomery, Sujal Saraiya, Timothy W.C. Ho, Harinder S. Garewal, James Wilson, Laszlo Lorand

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Several lines of evidence indicate that immunoglobulin-bound prolactin found in human serum is not a conventional complex between an anti-prolactin antibody and prolactin but a different type of association of prolactin with the Fab portion of IgG heavy chains. The complex of prolactin with IgG was purified from serum by anti-human prolactin affinity chromatography and was shown to contain close to 1 mole of N(ε)-(γ-glutamyl)lysine crosslinks per mole of complex, a characteristic feature in structures crosslinked by transglutaminase. Interestingly, the complex caused a proliferation of cells from a subset of patients with chronic lymphocytic leukemia, while it was inactive in a cell proliferation prolactin bioassay. By contrast, human prolactin stimulated the proliferation of cells in the bioassay but had no effect on the complex-responsive cells from the patients. Competition studies with prolactin and free Fc fragment of IgG demonstrated a necessity for engaging both the prolactin and the immunoglobulin receptors for proliferation. 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.

Original languageEnglish (US)
Pages (from-to)3278-3282
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number8
DOIs
StatePublished - Apr 11 1995

Keywords

  • chronic lymphocytic leukemia
  • isopeptide crosslinks
  • stimulant
  • transglutaminase

ASJC Scopus subject areas

  • General

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