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Related Experiment Videos

Idiotypic variation in a human B lymphoma cell line.

N Berinstein1, M J Campbell, K Lam

  • 1Department of Medicine/Oncology, Stanford University, CA 94305.

Journal of Immunology (Baltimore, Md. : 1950)
|January 15, 1990
PubMed
Summary

B cell lymphoma cells can change their surface immunoglobulin (Ig) markers, leading to antibody therapy resistance. This study identified specific rates of these Ig variations in lymphoma cell lines.

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • B cell lymphoma diagnosis and therapy often rely on unique surface immunoglobulin idiotype (Ig Id) markers.
  • Somatic gene variation in these Ig Id markers can lead to therapeutic resistance by evading anti-Id antibody recognition.

Purpose of the Study:

  • To investigate the occurrence and characteristics of idiotype variation in a B cell lymphoma cell line.
  • To quantify the rate of idiotype loss and immunoglobulin (Ig) expression loss in vitro.
  • To analyze the genetic and molecular basis of these variations.

Main Methods:

  • Utilized anti-idiotype (anti-Id) antibodies for screening lymphoma cell variants.
  • Employed fluorescence-activated cell sorting (FACS) for isolating cells with altered idiotype expression.

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  • Performed Southern blotting for Ig gene rearrangement analysis and immunoprecipitation for Ig chain alterations.

    • Main Results:

    • Identified idiotype variants at a rate of 2.7 x 10^-4/cell/generation and Ig- variants at 1.31 x 10^-5/cell/generation.
    • Subcloned variants showed altered reactivity to anti-Id antibodies, indicating subtle idiotype changes.
    • Southern blot confirmed clonal relationship, while immunoprecipitation revealed alterations in lambda-L chains but not mu-H chains.

    Conclusions:

    • Idiotype variation is an ongoing process in B cell lymphoma cell lines, impacting therapeutic targets.
    • Lambda-L chain gene rearrangement and expression contribute to observed idiotype alterations.
    • Understanding these variations is crucial for developing more effective antibody-based immunotherapies for B cell lymphomas.