Recombination of light chain genes

The  variable V region  of  a light  chain  is  encoded  through  a  separate  DNA sequence from which encoding the constant C region. These two segments lie on the similar chromosome but they are sited some way apart. In duration maturation of the B lymphocyte the C and V region DNAs are moved next to every other and are joined together to established a functioning light chain gene. This somatic recombination commonly occurs through deletion of the DNA among the germ-line V and C regions but can also occur in some cases through an inversion mechanism.

Figure: In the germ-line (embryo) DNA, sequences coding for the variable (V) region lie distant from those encoding the constant (C) region. During the differentiation of B lymphocytes, these two sequences are brought together to form an active antibody gene by deletion of the intervening DNA (somatic recombination).

In fact, the condition is rather more complex than this simple model defines. The germ-line V gene segment that is shown in the figure encodes only about the first 97 amino acids of the variable region of the light chain polypeptide.  The residual few amino acids of the light chain variable region (residues 98–110) are encoded through a piece of the DNA known as the J gene segment. This J segment must not be confused with the J chain in IgM pentamer.  In  germ-line  the  J  gene  segment  lies  just  upstream  of  the  C  gene segment and divided from it only through an intron. In addition, there are multiple J and V gene segments; in humans about 40 V and 5 J regions exist.

In during of B-lymphocyte differentiation, one of the 40 or so V regions becomes connected precisely to one of the J gene segments to establish a light chain gene. This somatic recombination procedure is known as V_J joining. In Figure, V₃ has been chosen for recombination and has connected to J₂. The Transcription now begin just upstream of the recombined V segment just upstream of V₃ and continues until the end of the C segment.  The another J segment  series  are also transcribed,  but these  series  are  lost  during  subsequent  RNA  splicing  which  erased  the intron upstream  of the C segment. Therefore the final mRNA holds only V₃J₂C sequences and encodes a corresponding light chain polypeptide.  Whole, about 200 several human κ light chains can be made through joining any one of the 40 V segments to any one of the J gene segments.

The λ light chain genes also arise through somatic recombination throughout maturation of the B lymphocyte but there are fewer J and V gene segments than for κ chain genes. Many antibody molecules have not λ light chains and κ light chains.