Copy choice mechanism of immunoglobulin heavy-chain switch recombination.

The immunoglobulin heavy-chain switch is mediated by a recombination event between DNA switch regions associated with donor and recipient constant-region genes. We have determined that the mutations which can be found in some switch regions after recombination appear to arise on only one strand of DNA. This result suggests that switch recombination involves error-prone synthesis of one DNA strand and ligation of the other strand from preexisting DNA.

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Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch

Molecular and Cellular Biology ◽

10.1128/mcb.9.5.1850-1856.1989 ◽

1989 ◽

Vol 9 (5) ◽

pp. 1850-1856

Author(s):

W Dunnick ◽

M Wilson ◽

J Stavnezer

Keyword(s):

Heavy Chain ◽

Recombination Event ◽

Point Mutations ◽

Immunoglobulin M ◽

Constant Region ◽

Switch Region ◽

Nucleotide Substitutions ◽

Region Gene ◽

Constant Region Gene ◽

Switch Regions

The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the mu and alpha constant region coding segments. Switch recombination to IgA expression results in a recombinant mu-alpha switch region upstream of the expressed alpha constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the expected products of simple mu to alpha switches. Five members of a third set of molecular clones share the same recombination site in both the mu and the alpha switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surprisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.

Download Full-text

Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch.

Molecular and Cellular Biology ◽

10.1128/mcb.9.5.1850 ◽

1989 ◽

Vol 9 (5) ◽

pp. 1850-1856 ◽

Cited By ~ 57

Author(s):

W Dunnick ◽

M Wilson ◽

J Stavnezer

Keyword(s):

Heavy Chain ◽

Recombination Event ◽

Point Mutations ◽

Immunoglobulin M ◽

Constant Region ◽

Switch Region ◽

Nucleotide Substitutions ◽

Region Gene ◽

Constant Region Gene ◽

Switch Regions

The heavy-chain switch from immunoglobulin M (IgM) expression to IgA expression is mediated by a recombination event between segments of DNA called switch regions. The switch regions lie two to six kilobases upstream of the mu and alpha constant region coding segments. Switch recombination to IgA expression results in a recombinant mu-alpha switch region upstream of the expressed alpha constant region gene. We have characterized the products of switch recombination by a lymphoma cell line, I.29. Two sets of molecular clones represent the expected products of simple mu to alpha switches. Five members of a third set of molecular clones share the same recombination site in both the mu and the alpha switch regions, implying that the five molecular clones were derived from a single switch recombination event. Surprisingly, the five clones fall into two sets of sequences, which differ from each other by several point mutations and small deletions. Duplication of switch region sequences are also found in these five molecular clones. An explanation for these data is that switch recombination involves DNA synthesis, which results in nucleotide substitutions, small deletions, and duplications.

Download Full-text