Vale Andre M, Nobrega Alberto, Schroeder Harry W
Program in Immunobiology, Carlos Chagas Filho Institute of Biophysics.
Department of Immunology, Paulo de Goes Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Ann N Y Acad Sci. 2015 Dec;1362(1):48-56. doi: 10.1111/nyas.12808. Epub 2015 Jun 23.
Because of N addition and variation in the site of VDJ joining, the third complementarity-determining region of the heavy chain (CDR-H3) is the most diverse component of the initial immunoglobulin antigen-binding site repertoire. A large component of the peritoneal cavity B-1 cell component is the product of fetal and perinatal B cell production. The CDR-H3 repertoire is thus depleted of N addition, which increases dependency on germ-line sequence. Cross-species comparisons have shown that DH gene sequence demonstrates conservation of amino acid preferences by reading frame. Preference for reading frame 1, which is enriched for tyrosine and glycine, is created both by rearrangement patterns and by pre-BCR and BCR selection. In previous studies, we have assessed the role of conserved DH sequence by examining peritoneal cavity B-1 cell numbers and antibody production in BALB/c mice with altered DH loci. Here, we review our finding that changes in the constraints normally imposed by germ-line-encoded amino acids within the CDR-H3 repertoire profoundly affect B-1 cell development, especially B-1a cells, and thus natural antibody immunity. Our studies suggest that both natural and somatic selection operate to create a restricted B-1 cell CDR-H3 repertoire.
由于N的添加以及VDJ连接位点的变化，重链的第三个互补决定区（CDR-H3）是初始免疫球蛋白抗原结合位点库中最多样化的组成部分。腹膜腔B-1细胞成分的很大一部分是胎儿期和围生期B细胞产生的产物。因此，CDR-H3库缺乏N的添加，这增加了对种系序列的依赖性。跨物种比较表明，DH基因序列通过阅读框显示出氨基酸偏好的保守性。对富含酪氨酸和甘氨酸的阅读框1的偏好是由重排模式以及前B细胞受体（pre-BCR）和B细胞受体（BCR）选择产生的。在先前的研究中，我们通过检查DH基因座改变的BALB/c小鼠的腹膜腔B-1细胞数量和抗体产生，评估了保守DH序列的作用。在这里，我们回顾我们的发现：CDR-H3库中种系编码氨基酸通常施加的限制的变化深刻影响B-1细胞发育，尤其是B-1a细胞，从而影响天然抗体免疫。我们的研究表明，自然选择和体细胞选择都在起作用，以创建一个受限的B-1细胞CDR-H3库。
