V(D)J Recombination, Somatic Hypermutation and Class Switch Recombination of Immunoglobulins: Mechanism and Regulation.

Abstract

Immunoglobulins (Ig) emerged from B lymphocytes, capable of recognizing almost all kinds of antigens owing to the extreme diversity of their antigen binding portions known as variable (V) regions, plays an important role in immune response. The exons encoding the V regions are known as V (variable), D (diversity), J (joining) genes. V, D, J segments exist as multiple copy arrays on the chromosome. The recombination of V(D)J gene are the key mechanism to produce antibody diversity. The recombinational process including randomly choosing a pair of V, D, J segments, introducing double strand-breaks (DSBs) adjacent to each segment, deleting (or inverting in some cases) the intervening DNA and ligating the segments together is defined as V(D)J recombination, which contributes to surprising Ig diversity in vertebrate immune system. To enhances both the ability of immunoglobulins to recognize and bind to foreign antigens and the effector capacities of the expressed antibodies, naive B cells will undergo class switching recombination (CSR) and somatic hypermutation (SHM). However, the genetics mechanisms of V(D)J recombination, CSR and SHM are not entirely clearly. In this review, we summarize the major progression about mechanism studies of immunoglobulin V(D)J gene recombination and CSR as well as SHM and their regulatory mechanisms.