 |
|
Title
|
|
Somatic variants of murine immunoglobulin lambda light chains.
|
|
|
Authors
|
|
A.L.Bothwell,
M.Paskind,
M.Reth,
T.Imanishi-Kari,
K.Rajewsky,
D.Baltimore.
|
|
|
Ref.
|
|
Nature, 1982,
298,
380-382.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Studies of the murine lambda light chains produced by myeloma cells provided the
first evidence for somatic point mutation of germ-line variable (V) region
genes. An examination of the variable regions of 19 lambda 1 chains revealed
seven which differed from a common sequence by one to three amino acid
substitutions. Subsequently, one of these presumed somatic variants of the
single lambda 1 V gene was characterized by DNA sequence analysis of the
rearranged functional gene. The predicted DNA sequence alteration was observed
and no silent mutation was evident. These studies of lambda chain variants
suggested that the hypervariable, complementarity-determining regions (CDRs) ht
be a preferred site of somatic mutation because all seven characterized variants
contained substitutions only in these regions. By contrast, comparisons of
closely related kappa chain variable region amino acid sequences, and more
recently VK and VH genes, have suggested that somatic mutation probably occurs
in codons for both framework and CDR residues. To examine this apparent
discrepancy between the sites of somatic mutations in lambda and kappa genes, we
have determined the nucleotide sequence of two lambda 1 gene from hybridomas and
a lambda 2 gene from a myeloma. These sequences demonstrate that somatic
mutation in lambda genes can occur in both the framework and CDR residues.
|
|
|
|