Immunoglobulin Gene Rearrangements, Oncogenic Translocations, B-Cell Receptor Signaling, and B Lymphomagenesis

  • Murali Gururajan
  • Subbarao Bondada
Part of the Cancer Genetics book series (CANGENETICS)


Reciprocal chromosomal translocations involving one of the immunoglobulin (Ig) loci and a proto-oncogene are a hallmark of many types of B-cell lymphoma (Vanasse et al. 1999). As a consequence of such translocations, the oncogene comes under the control of the active Ig locus, causing a deregulated, constitutive expression of the oncogene. Examples of such translocations include Bcl-2-IgH translocation associated with follicular lymphoma, Bcl-6-IgH associated with diffuse large B-cell lymphoma, c-Myc translocation associated with Burkitt’s lymphoma, and Pax-5 translocation associated with marginal zone and large cell lymphomas. Dysregulated expression of oncogenes often affects lymphoma growth by altering the expression of key genes that lie downstream of BCR – for example, the ability of Pax-5 to promote lymphomagenesis correlated with expression of components of BCR signaling pathway, including upregulation of Igα and CD19 antigens and downregulation of BCR-negative regulators, such as CD22 and PIR-B (Cozma et al. 2007). Despite translocations involving Ig locus, majority of the B-cell lymphomas retain functional B-cell receptor (Kuppers and Dalla-Favera 2001; Kuppers 2005) and disruption of the B-cell receptor expression inhibited their growth (Gururajan et al. 2006). In addition, somatic hypermutation, a process involving random mutations in the Ig variable regions unique to B cells, generates B-cell receptors of higher affinity even as lymphoma cells continue to divide. The mutated BCRs seem to retain their function as evidenced by hyperactive signaling molecules downstream of the BCR, including constitutive phosphorylation of several key tyrosine kinases and MAP kinases (Gururajan et al. 2005, 2006, 2007). The importance of BCR signaling in B-cell lymphomas in the context of IgH translocations is described below.


Pylorus Infection Follicular Lymphoma Malt Lymphoma Lymphoma Growth 
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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Pathology – DSBEmory UniversityAtlantaUSA
  2. 2.Department of MicrobiologyImmunology and Molecular Genetics, Markey Cancer Center, University of KentuckyLexingtonUSA

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