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8 - Immunoglobulin and T-cell receptor gene rearrangements

from Part II - Cell biology and pathobiology

Published online by Cambridge University Press:  01 July 2010

By
Jacques J. M. van Dongen  and
Anton W. Langerak
Edited by
Ching-Hon Pui
Jacques J. M. van Dongen
Affiliation:
Professor, Department of Immunology, Erasmus University Rotterdam, Rotterdam, the Netherlands
Anton W. Langerak
Affiliation:
Department of Immunology, Erasmus University Rotterdam, Rotterdam, the Netherlands
Ching-Hon Pui
Affiliation:
St. Jude Children's Research Hospital, Memphis
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Summary

Introduction

The ability of the immune system to specifically recognize millions of different antigens and antigenic epitopes is based on the enormous diversity (at least 10) of antigen-specific receptors, that is, surface membrane-bound immunoglobulin (SmIg) molecules on B lymphocytes and T-cell receptor (TCR) molecules on T lymphocytes. The antigen-specific receptors differ from lymphocyte to lymphocyte, but each single lymphocyte or lymphocyte clone expresses approximately 10 receptors with identical antigen specificity. The extensive diversity of the antigen-specific receptors of lymphocytes is based on rearrangement processes in the Ig/TCR-encoding genes.

Since the various types of lymphoid leukemias resemble normal lymphoid (precursor) cells, most lymphoid leukemias and lymphomas also contain rearranged IG/TCR genes. Being derived from a single malignantly transformed lymphoid cell, all cells of a lymphoid malignancy have their IG/TCR genes rearranged in an identical way. This information can be readily employed for clonality assessment in lymphoproliferations. We will discuss the IG/TCR gene rearrangement processes and the methods for detecting clonal IG/TCR gene rearrangements in various types of (childhood) leukemia. Finally, several applications of diagnostic clonality studies in childhood leukemia are presented.

IG/TCR gene rearrangement processes

Ig molecules and their encoding genes

Ig molecules consist of two disulfide-bonded Ig heavy (IgH) chains and two Ig light chains. The Ig class or subclass is determined by the isotype of the involved IgH chain, irrespective of the type of light chain. Each B lymphocyte or B-lymphocyte clone expresses only one type of light chain (Igκ or Igλ), whereas multiple IgH chains can be expressed.

Type
Chapter
Information
Childhood Leukemias , pp. 210 - 234
Publisher: Cambridge University Press
Print publication year: 2006

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