Department of Biological Sciences, University of Alberta, Edmonton, T6G-2E5 Canada.
Dev Comp Immunol. 2010 Jun;34(6):669-76. doi: 10.1016/j.dci.2010.01.013. Epub 2010 Feb 4.
It has long been held that the cold-blooded vertebrates lack mammalian-like germinal centers, though they do have affinity maturation and the immunoglobulin mutator activation-induced cytidine deaminase or AID. Using AID as a marker of sites of somatic hypermutation, we have identified discrete cell clusters of up to several thousand cells, in the spleen and kidney of channel catfish (Ictalurus punctatus), which may be primordial germinal centers. In situ hybridization revealed that AID expressing cells are interspersed or surrounded by a population of pigmented CSF1-R expressing cells called melano-macrophages. Significantly, melano-macrophages or associated reticular cells have been previously noted for their ability to retain soluble antigen on or near their surface for several weeks following vaccination. Laser capture microdissection and RT-PCR were used to establish that these cell clusters also contained cells expressing Ig heavy chain transcripts as well as transcripts of TcRbeta and the putative CD4 homologue of fish. These observations, coupled with past work showing that mutations develop in B-cell lineages in fishes, allow us to develop a model for how affinity maturation may have evolved in early gnathostome vertebrates.
长期以来一直认为冷血脊椎动物缺乏类似哺乳动物的生发中心，尽管它们确实具有亲和力成熟和免疫球蛋白突变激活诱导胞苷脱氨酶或 AID。使用 AID 作为体细胞超突变位点的标志物，我们已经在鲶鱼（Ictalurus punctatus）的脾脏和肾脏中鉴定出多达几千个细胞的离散细胞簇，这些细胞簇可能是原始生发中心。原位杂交显示，表达 AID 的细胞散布或被一群称为黑素巨噬细胞的着色 CSF1-R 表达细胞包围。重要的是，黑素巨噬细胞或相关的网状细胞因其能够在接种后数周内在其表面或附近保留可溶性抗原的能力而被先前注意到。激光捕获显微切割和 RT-PCR 用于确定这些细胞簇还含有表达 Ig 重链转录本以及 TcRbeta 和鱼类潜在 CD4 同源物转录本的细胞。这些观察结果，加上过去的工作表明鱼类的 B 细胞谱系中会发生突变，使我们能够建立一个模型，说明亲和力成熟如何在早期颌脊椎动物中进化。
