**Hematological Malignancies**

**Chapter 2**

**Provisional chapter**

**The Antigen Receptor as a Driver of B-Cell Lymphoma**

The expression of a functional antigen receptor is necessary for cell survival of normal B lymphocytes and most B-cell neoplasms alike. When the genetic modifications of the B-cell receptor locus fail to produce a functional antigen receptor or result in deleterious mutations of a previously expressed receptor, the affected B cell will undergo apoptosis. The three physiological mechanisms that generate the B-cell receptor, VDJ recombination, somatic hypermutation, and class switch recombination, can induce double-strand DNA breaks and can specifically contribute to lymphomagenesis. On the other hand, the B-cell receptor activation and signaling pathways, which provide strong survival and proliferation signals to normal B cells, can support the growth and evolution of malignant lymphocytes. As a result, an otherwise structurally normal B-cell receptor can behave, from the functional perspective, as a true oncogene. In this chapter, we provide an in-depth discussion of the most recently discovered recurrent mechanisms involving the B-cell receptor in lymphoma pathogenesis. The discussion is structured around two major topics: (1) the genetic mechanisms that create a functional antigen receptor and their errors leading to oncogenic events, and (2) the pathogenic activation of the B-cell receptor signaling cascade. Finally, we will briefly comment on novel emerging therapies targeting the B-cell receptor at different levels.

**The Antigen Receptor as a Driver of B-Cell Lymphoma** 

DOI: 10.5772/intechopen.72122

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

The immune system has evolved with the primary purpose of eliminating or at least controlling invading pathogens. In contrast to innate immunity, the adaptive immune system relies

**Keywords:** lymphoma, B-cell receptor, activation-induced deaminase (AID),

somatic hypermutation, class switch recombination, lymphomagenesis, pathogenesis,

**Development and Evolution**

**Development and Evolution**

Marcelo A. Navarrete

**Abstract**

oncogenesis

**1. Introduction**

Marcelo A. Navarrete

Julieta Sepulveda, Noé Seija, Pablo Oppezzo and

Julieta Sepulveda, Noé Seija, Pablo Oppezzo and

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72122

**Provisional chapter**
