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Publication : Junctional diversification in the generation of the precursor of a discrete immune response.

First Author  George J Year  1993
Journal  Mol Immunol Volume  30
Issue  4 Pages  395-402
PubMed ID  7681150 Mgi Jnum  J:42517
Mgi Id  MGI:1095901 Doi  10.1016/0161-5890(93)90069-n
Citation  George J, et al. (1993) Junctional diversification in the generation of the precursor of a discrete immune response. Mol Immunol 30(4):395-402
abstractText  Phosphocholine (PC)-specific antibodies that arise in the mouse in response to Proteus morganii (PM) and use V1-DFL16.1-JH1 are characterized by a number of recurring mutations. Most striking is an invariant A for G substitution in codon 95 of VH which results in an asparagine instead of aspartate at that position. Because of the apparent importance of this substitution in an anti-PC(PM) response, we wanted to determine the molecular basis for this base change. A cDNA library derived from pre-immune splenic B cells was examined for the frequency of VDJ containing the A substitution at 95 and the presence of additional point mutations in these sequences. Six different cDNA were isolated which contained an A substitution at the VD junction (frequency 0.00009); a seventh positive cDNA could not be examined. The V segments of four of these cDNA matched known germline genes and were, therefore, unmutated. Two others closely matched V in families whose members have not all been characterized, hence, it is not known whether the mutations observed are somatic or germline in origin. Sequences of 35 cDNA clones, containing the same V segment but differing in D, J and junctional nucleotides, revealed no mutations. These results indicate that the A substitution generated at codon 95 is most likely a product of V-DJ joining.
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