In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 5 ( 1999-03-02), p. 2262-2267
Abstract:
Antibodies to phosphatidylcholine (PtC), a common constituent of mammalian and bacterial cell membranes, represent a large proportion of the natural antibody repertoire in mice. Previous studies of several mouse strains (e.g., C57BL/6) have shown that anti-PtC antibodies are mainly encoded by the V H 11 and V H 12 immunoglobulin heavy chain variable region gene families. We show here, however, that V H 11 and V H 12 encode only a small proportion of the anti-PtC antibodies in BALB/c mice. Instead, V H Q52-encoded antibodies predominate in this strain. In addition, two-thirds of the cells expressing V H Q52 family genes use a single gene (which, interestingly, has been previously shown to predominate in the anti-oxazolone response). We also show here that in anti-PtC antibodies from all strains, the distinctive antigen-binding sites associated with V H Q52 differ substantially from those associated with V H 11 and V H 12. That is, V H Q52-containing transcripts preferentially use the joining region J H 4 rather than J H 1 and exhibit more diverse complementarity-determining region 3 (CDR3) junctions with more N-region nucleotide additions at the gene segment junctions. Thus, the V H gene family that predominates in the anti-PtC repertoire differs among mouse strains, whereas the distinctive V H DJ H rearrangements (CDR3, J H ) associated with each V H gene family are similar in all strains. We discuss these findings in the context of a recent hypothesis suggesting that CDR3 structure, independent of V H framework, is sufficient to define the specificity of an antibody.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.96.5.2262
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1999
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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