V2

AAAAAAA Mature mRNA

21.17 Antibody diversity is produced by somatic recombination. Shown here is recombination among gene segments that encode the human kappa light chain.

AAAAAAA Mature mRNA

different functional V gene segments, 5 different J genes, and a single C gene segment, all of which are present in the germ-line DNA (IFigure 21.17a). The V gene segments, which are about 400 bp in length, are located on the same chromosome and are separated from one another by about 7000 bp. The J gene segments are about 30 bp in length and all together encompass about 1400 bp.

Initially, an immature lymphocyte inherits all of the V gene segments and all of the J gene segments present in the germ line. In the maturation of the lymphocyte, somatic recombination within a single chromosome moves one of the V genes to a position next to one of the J gene segments (IFigure 21.17b). In Figure 21.17b, V2 (the second of approximately 35 different V gene segments) undergoes somatic recombination, which places it next to J3 (the third of 5 J gene segments); the intervening segments are lost.

After somatic recombination has taken place, the combined V-J-C gene is transcribed and processed (I Figure 21.17c and d). The mature mRNA that results contains only sequences for a single V, J, and C segment; this mRNA is translated into a functional light chain (I Figure 21.17e).

In this way, each mature human B cell produces a unique type of kappa light chain, and different B cells produce slightly different kappa chains, depending on the combination of V and J segments that are joined.

The gene that encodes the lambda light chain is organized in a similar way but differs from the kappa gene in the number of copies of the different segments. In the human gene for the lambda light chain, there are from 29 to 33 different functional V gene segments and 4 or 5 different functional J and C gene segments (each C gene segment is attached to a different J segment). Somatic recombination takes place among the segments in the same way as that in the kappa gene, generating many possible combinations of lambda light chains.

The gene that encodes the immunoglobulin heavy chain is arranged in V, J, and C segments, but this gene also possesses D (for diversity) segments. Somatic recombination taking place in lymphocyte maturation joins one D gene segment to one J gene segment, and then a V gene segment is joined to this combined D-J gene segment (iFigure 21.18a and b). Transcription and RNA processing of this gene produces a mRNA that encodes only one

The germ-line DNA contains multiple V, D, J and C gene segments.

^ In somatic recombination, V, D, J, and C segments are joined to produce the DNA found in the B cell.

C7/C8 C9 line DNA

Somatic recombination

C4 C5

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