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Related Experiment Videos

Familial macroglobulinaemia: hyperactive B-cells but normal natural killer function

H M Ogmundsdóttir1, G M Jóhannesson, S Sveinsdóttir

  • 1Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.

Scandinavian Journal of Immunology
|August 1, 1994
PubMed
Summary

This study found B cell hyperreactivity in an Icelandic family with a history of B cell malignancies. Asymptomatic members showed increased immunoglobulin production, suggesting a hereditary tendency.

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Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • A family with a history of monoclonal gammopathies and B cell malignancies exhibited familial clustering.
  • Previous studies noted elevated serum IgM in nine family members, with some cases progressing to multiple myeloma and Waldenström's macroglobulinaemia.

Purpose of the Study:

  • To investigate the immunological characteristics of family members with a hereditary predisposition to B cell malignancies.
  • To identify potential B cell abnormalities in asymptomatic individuals within the affected family.

Main Methods:

  • In vitro immunoglobulin production assays were performed on 35 family members and 13 healthy controls.
  • Immunoglobulin production was measured at baseline and after stimulation with pokeweed mitogen (PWM).

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  • Proliferative responses to PWM and serum levels of interleukin-4 were assessed. Natural Killer (NK) cell function was also evaluated.

    • Main Results:

    • Baseline immunoglobulin production was normal, but mean production of all immunoglobulin classes (IgM, IgG, IgA) was significantly increased in response to PWM stimulation (P < 0.05).
    • Ten family members displayed markedly increased immunoglobulin production, with no isolated elevation of IgM, indicating intact class switching.
    • No significant increase in proliferative responses to PWM or evidence of depressed NK function was found. Serum IL-4 levels were normal in tested individuals.

    Conclusions:

    • The study identified B cell hyperreactivity in asymptomatic family members, suggesting a hereditary component contributing to the observed B cell malignancies.
    • These findings highlight a potential B cell abnormality that may predispose individuals to lymphoproliferative disorders within this family.
    • No evidence of defects in regulatory mechanisms or impaired NK cell function was observed, pointing towards intrinsic B cell hyperactivity.