B-cell IGH Recombinations

In 1987 S. Tonegawa (Japan, USA) won the Nobel Prize for the research on the genetic mechanisms of antibody diversity.

After antigenic stimulation and priming the primed B cell DNA is composed of a final gene repertoire to be transcripted onto mRNA and translated onto a peptide chain. During isotype switching, IgM's H chain must be replaced by a selection of the Cγ, Cα or Cε gene, which is achieved by the use of switch regions. Antibody diversity allows the immune system to structurally specify the antigen-binding sites of an antibody to a causative antigen. During an advanced B-cell-mediated immune response, antibody diversity is generated by the following mechanisms:
(1) A large number of V genes is achieved in the course of B lymphopoiesis.
(2) Combinatorial association may be explained by different combinations of H chains and L chains within a single B cell.
(3) Junctional diversity is linked to a random manner of joining the VJ and VDJ regions. In addition, during the joining of the VJ and VDJ regions inaccuracies may take place.
(4) N region insertion between the VJ and VDJ regions occurs when a series of nucleotides is catalyzed by the enzyme terminal transferase that leads to forming a new hypervariable region.
(5) Somatic hypermutation occurs only in the V genes of B cells. Somatic hypermutation results in approximately one nucleotide change per V gene, per cell division.