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What is somatic recombination?

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Somatic recombination refers to the process involving the formation of immunoglobin genes through recombination of the germline genetic elements, or segments of immunoglobin gene, within a single locus. This process occurs in the primary lymphoid tissue, which is the bone marrow for B cells and Thymus for T cells. Somatic recombination precedes antigen contact, and occurs during B cell development in the bone marrow.

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In mammals, immunoglobin gene segments are arranged in groups of variable (V), diversity (D), joining (J) and constant (C) exons. In vertebrate lymphocytes, somatic recombination nearly randomly combines Variable, Diverse and Joining gene segments. Random choices of different genes result into diverse encoding of proteins, matching antigens from bacteria, parasites, viruses, dysfunctional cells and pollens.

One DH and one JH are randomly spliced with the removal of all intervening DNA (D-J joining). This is followed by random splicing of VH segment to the rearranged DJH segment. The intervening sequences between VDJH and CH are transcribed into primary mRNA. In the nucleus, the splicing of the primary mRNA produces mature message, which is translated into H chain when transported in the cytoplasm. Human DNA for H chain has about 50 functional VH segments, 30 DH segments and six JH segments. The first two CDR and three FR of the heavy chain variable region undergo encoding by VH.

Random formation of many diverse VJL and VDJH combinations generate combinatorial diversity. On the other hand, the imprecise joining of gene segments and addition of nucleotides to the DNA sequence splice sites results into junctional diversity.

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