Predominant V 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, Katherine J., Wilshire, Jennifer A., MacKenzie, John D., Kantor, Aaron B., Herzenberg, Leonard A., Herzenberg, Leonore A.
• Format: Journal Article
• Language: English
• Published: 02.03.1999
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.5.2262

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.