Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites.
Predominant VH genes expressed in innate antibodies are associated with distinctive antigen-binding sites.
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先天抗体中表达的主要 VH 基因与独特的抗原结合位点相关。
DOI：
10.1073/pnas.96.5.2262
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发表时间：
1999
影响因子：
11.1
通讯作者：
Herzenberg,LA
中科院分区：
文献类型：
--
作者：
Seidl,KJ;Wilshire,JA;MacKenzie,JD;Kantor,AB;Herzenberg,LA;Herzenberg,LA
磷脂酰胆碱（PtC）是哺乳动物和细菌细胞膜的常见成分，其抗体在小鼠天然抗体库中占很大比例。先前对几种小鼠品系的研究（例如，C57BL/6）已经显示抗PtC抗体主要由VH11和VH12免疫球蛋白重链可变区基因家族编码。然而，我们在这里显示，VH11和VH12编码的抗PtC抗体在BALB/c小鼠中仅占一小部分。相反，VHQ 52编码的抗体在该菌株中占主导地位。此外，三分之二表达VHQ 52家族基因的细胞使用单个基因（有趣的是，先前已显示其在抗恶唑酮反应中占主导地位）。我们在这里还表明，在来自所有菌株的抗PtC抗体中，与VHQ 52相关的独特抗原结合位点与与VH 11和VH 12相关的抗原结合位点有很大不同。也就是说，含有VHQ 52的转录物优先使用连接区JH4而不是JH1，并且在基因片段连接处具有更多N区核苷酸添加的更多样的互补决定区3（CDR 3）连接。因此，在抗PtC库中占优势的VH基因家族在小鼠品系之间不同，而与每个VH基因家族相关的独特的VH/H重排（CDR 3，JH）在所有品系中是相似的。我们讨论了这些发现的背景下，最近的假设表明，CDR 3结构，独立的VH框架，是足以定义抗体的特异性。
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 VHgene family that predominates in the anti-PtC repertoire differs among mouse strains, whereas the distinctive VHDJHrearrangements (CDR3, JH) associated with each VHgene family are similar in all strains. We discuss these findings in the context of a recent hypothesis suggesting that CDR3 structure, independent of VHframework, is sufficient to define the specificity of an antibody.