Predominant V sub(H) genes expressed in innate antibodies are associated with distinctive antigen-binding sites

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 96; no. 5; pp. 2262 - 2267
• Main Authors: Seidl, K J, Wilshire, JA, MacKenzie, J D, Kantor, AB, Herzenberg, LA
• Format: Journal Article
• Language: English
• Published: 02.03.1999
• ISSN: 0027-8424

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 sub(H)11 and V sub(H)12 immunoglobulin heavy chain variable region gene families. We show here, however, that V sub(H)11 and V sub(H)12 encode only a small proportion of the anti-PtC antibodies in BALB/c mice. Instead, V sub(H)Q52-encoded antibodies predominate in this strain. In addition, two-thirds of the cells expressing V sub(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 sub(H)Q52 differ substantially from those associated with V sub(H)11 and V sub(H)12. That is, V sub(H)Q52- containing transcripts preferentially use the joining region J sub(H)4 rather than J sub(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 sub(H) gene family that predominates in the anti- PtC repertoire differs among mouse strains, whereas the distinctive V sub(H)DJ sub(H) rearrangements (CDR3, J sub(H)) associated with each V sub(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 sub(H) framework, is sufficient to define the specificity of an antibody.