Hairy cells from hairy cell leukemia patients presenting with pronounced polyclonal hypergammaglobulinemia secrete a...

Area of Science:

• Immunology
• Hematology
• Cell Biology

Background:

• Hairy cell leukemia (HCL) is a rare B-cell malignancy.
• Pronounced polyclonal hypergammaglobulinemia (PPH) is a clinical feature in some HCL patients.
• The immunological function of hairy cells in PPH pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the role of hairy cells in PPH.
• To identify factors secreted by hairy cells that influence immunoglobulin production.
• To elucidate the cellular mechanisms involved in IgG synthesis induction.

Main Methods:

• Collection and conditioning of medium from HCL patient hairy cells (HCCM).
• Assay of IgG production by normal peripheral blood mononuclear cells (PBMCs) cultured with HCCM.
• T cell depletion and cell separation techniques (0.4-micron membrane, monoclonal antibodies to HLA-DR and CD3).
• Analysis of HCCM for growth factors (IL-1, IL-6) and molecular weight fractionation.

Main Results:

• HCCM from HCL patients with PPH significantly augmented IgG production by normal PBMCs in a dose-dependent manner.
• HCCM from HCL patients without PPH had no effect on IgG production.
• HCCM-induced IgG synthesis required T-B cell interactions, as it was abrogated by T cell depletion, cell separation, and antibodies to CD3 and HLA-DR.
• No B cell growth factor, IL-1, or IL-6 activity was detected in HCCM.
• IgG-inducing activity was localized to fractions of 5000-8000 Da in HCCM.

Conclusions:

• Hairy cells from HCL patients with PPH secrete a novel factor that induces IgG synthesis.
• The induction of IgG synthesis by this factor necessitates T-B cell interactions involving the T cell receptor/CD3 complex and MHC class II antigens.
• This hairy cell-derived factor may be crucial in the pathogenesis of pronounced polyclonal hypergammaglobulinemia in HCL.