Das Sabyasachi, Fontenla-Iglesias Francisco, Hirano Masayuki, Morimoto Ryo, Au-Yeung Byron B, Wang Yashuo, Li Weiming, Boehm Thomas, Rast Jonathan P, Cooper Max D
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Emory Vaccine Center, Emory University, Atlanta, GA, USA.
Nat Commun. 2025 Jul 15;16(1):6503. doi: 10.1038/s41467-025-61187-1.
All extant jawless vertebrates (lampreys and hagfishes) possess a unique adaptive immune system characterized by highly variable lymphocyte receptors (VLR) that are assembled in developing lymphocytes using leucine-rich-repeat donor cassettes. Five VLR types have been identified in lampreys: VLRA, VLRB, VLRC, VLRD, and VLRE. VLRB-expressing lymphocytes are functional analogs to B cells, whereas VLRA, VLRC, VLRD, and VLRE-expressing lymphocytes are more akin to T cells of jawed vertebrates. Here we define an additional VLR, designated VLRF. VLRF is phylogenetically closest to VLRA, with which it likely shares a common ancestral gene of at least 250 million years in the past. VLR assembly analyses show that VLRA, VLRC, VLRD, VLRE, and VLRF share donor cassettes through long-range intra- and inter-chromosomal interactions, whereas VLRB utilizes a distinct, dedicated cassette set. The pattern of gene expression, donor cassette usage, and distinctive amino acid composition in the C-terminal stalk suggest that VLRF⁺ lymphocytes may represent an additional T-like sub-lineage, adding further complexity to the VLR-based adaptive immune system.
所有现存的无颌脊椎动物（七鳃鳗和盲鳗）都拥有独特的适应性免疫系统，其特征是高度可变的淋巴细胞受体（VLR），这些受体在发育中的淋巴细胞中利用富含亮氨酸重复序列的供体盒组装而成。在七鳃鳗中已鉴定出五种VLR类型：VLRA、VLRB、VLRC、VLRD和VLRE。表达VLRB的淋巴细胞是B细胞的功能类似物，而表达VLRA、VLRC、VLRD和VLRE的淋巴细胞更类似于有颌脊椎动物的T细胞。在这里，我们定义了另一种VLR，命名为VLRF。VLRF在系统发育上最接近VLRA，它们可能在至少2.5亿年前拥有共同的祖先基因。VLR组装分析表明，VLRA、VLRC、VLRD、VLRE和VLRF通过远距离的染色体内和染色体间相互作用共享供体盒，而VLRB则利用一套独特的专用盒。基因表达模式、供体盒使用情况以及C末端茎中的独特氨基酸组成表明，VLRF⁺淋巴细胞可能代表另一种T样亚谱系，这进一步增加了基于VLR的适应性免疫系统的复杂性。
