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Publication : Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites.

First Author  Seidl KJ Year  1999
Journal  Proc Natl Acad Sci U S A Volume  96
Issue  5 Pages  2262-7
PubMed ID  10051629 Mgi Jnum  J:53357
Mgi Id  MGI:1332339 Doi  10.1073/pnas.96.5.2262
Citation  Seidl KJ, et al. (1999) Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites. Proc Natl Acad Sci U S A 96(5):2262-7
abstractText  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 VH11 and VH12 immunoglobulin heavy chain variable region gene families. We show here, however, that VH11 and VH12 encode only a small proportion of the anti-PtC antibodies in BALB/c mice. Instead, VHQ52-encoded antibodies predominate in this strain. In addition, two-thirds of the cells expressing VHQ52 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 VHQ52 differ substantially from those associated with VH11 and VH12. That is, VHQ52-containing transcripts preferentially use the joining region JH4 rather than JH1 and exhibit more diverse complementarity-determining region 3 (CDR3) junctions with more N-region nucleotide additions at the gene segment junctions. Thus, the VH gene family that predominates in the anti-PtC repertoire differs among mouse strains, whereas the distinctive VHDJH rearrangements (CDR3, JH) associated with each VH gene family are similar in all strains. We discuss these findings in the context of a recent hypothesis suggesting that CDR3 structure, independent of VH framework, is sufficient to define the specificity of an antibody.
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