Vasconcellos R, Nobrega A, Haury M, Viale A C, Coutinho A
Unité d'Immunobiologie, CNRS URA 1961, Institut Pasteur, Paris, France.
Eur J Immunol. 1998 Mar;28(3):1104-15. doi: 10.1002/(SICI)1521-4141(199803)28:03<1104::AID-IMMU1104>3.0.CO;2-O.
Global analysis of natural antibody repertoires has revealed a marked conservation of reactivity patterns within inbred mouse strains, and characteristic strain-specific differences. We have now analyzed the genetic control of reactivity repertoires, aiming at identifying the respective selection mechanisms. Multiparametric statistics of a large number of serum antibody reactivities scored by quantitative Western blot analyses using extracts from homologous tissues and bacteria readily distinguish the reactivity patterns of C57BL/6 and BALB/c, revealing homogeneity among genetically identical individuals. Antibody repertoires in the prototype strains can also be segregated from those expressed by the respective IgH congenics, BC.8 and CB.20, demonstrating that IgH-linked genes contribute to determining natural antibody repertoires. Conversely, strains sharing IgH haplotype also express distinct reactivity patterns, indicating that other genes participate in the selection of serum IgM repertoires. Two such non-IgH loci were now identified. Thus, analysis of four MHC-congenic strains demonstrated that MHC-linked control of natural antibody repertoires is likely to operate through differential selection of T cell repertoires, since (1) mice that are congenic at the TCR beta locus, and (2) BALB/c nude mice grafted at birth with pure thymic epithelium from either C57BL/6 or BALB/c also differ in their natural antibody repertoires.
对天然抗体库的全球分析揭示了近交系小鼠品系内反应模式的显著保守性以及特征性的品系特异性差异。我们现在分析了反应库的遗传控制，旨在确定各自的选择机制。使用来自同源组织和细菌的提取物通过定量蛋白质印迹分析对大量血清抗体反应性进行多参数统计，很容易区分C57BL/6和BALB/c的反应模式，揭示了基因相同个体之间的同质性。原型品系中的抗体库也可以与各自的IgH同源系BC.8和CB.20所表达的抗体库区分开来，这表明与IgH连锁的基因有助于确定天然抗体库。相反，共享IgH单倍型的品系也表现出不同的反应模式，表明其他基因参与血清IgM库的选择。现在已经鉴定出两个这样的非IgH基因座。因此，对四个MHC同源系品系的分析表明，MHC对天然抗体库的连锁控制可能是通过对T细胞库的差异选择来实现的，因为（1）在TCRβ基因座上同源的小鼠，以及（2）出生时移植了来自C57BL/6或BALB/c的纯胸腺上皮的BALB/c裸鼠，它们的天然抗体库也不同。
