Stereotyped B Cell Receptor Immunoglobulins in B Cell Lymphomas

Methods Mol Biol. 2019;1956:139-155. doi: 10.1007/978-1-4939-9151-8_7.

Abstract

Comprehensive analysis of the clonotypic B cell receptor immunoglobulin (BcR IG) gene rearrangement sequences in patients with mature B cell neoplasms has led to the identification of significant repertoire restrictions, culminating in the discovery of subsets of patients expressing highly similar, stereotyped BcR IG. This finding strongly supports selection by common epitopes or classes of structurally similar epitopes in the ontogeny of these tumors. BcR IG stereotypy was initially described in chronic lymphocytic leukemia (CLL), where the stereotyped fraction of the disease accounts for a remarkable one-third of patients. However, subsequent studies showed that stereotyped BcR IG are also present in other neoplasms of mature B cells, including mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). Subsequent cross-entity comparisons led to the conclusion that stereotyped IG are mostly "disease-specific," implicating distinct immunopathogenetic processes. Interestingly, mounting evidence suggests that a molecular subclassification of lymphomas based on BcR IG stereotypy is biologically and clinically relevant. Indeed, particularly in CLL, patients assigned to the same subset due to expressing a particular stereotyped BcR IG display remarkably consistent biological background and clinical course, at least for major and well-studied subsets. Thus, the robust assignment to stereotyped subsets may assist in the identification of mechanisms underlying disease onset and progression, while also refining risk stratification. In this book chapter, we provide an overview of the recent BcR IG stereotypy studies in mature B cell malignancies and outline previous and current methodological approaches used for the identification of stereotyped IG.

Keywords: Antigen; Bioinformatics; Immunoglobulin gene; Pattern; Stereotypy; Subset; VH CDR3.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / genetics
  • Genes, Immunoglobulin*
  • Humans
  • Immunoglobulin Variable Region / chemistry
  • Immunoglobulin Variable Region / genetics
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Receptors, Antigen, B-Cell / chemistry
  • Receptors, Antigen, B-Cell / genetics*

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Variable Region
  • Receptors, Antigen, B-Cell