Bukhari Ameera M, Meng Wenzhao, Rosenfeld Aaron M, Prak Eline T Luning, Knight Katherine L
Department of Microbiology and Immunology, Loyola University Chicago, 2160 S. First Ave, Maywood, IL, 60153, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 405B Stellar Chance Labs, 422 Curie Blvd., Philadelphia, PA, 19104, USA.
Sci Rep. 2025 Jul 22;15(1):26613. doi: 10.1038/s41598-025-11209-1.
Human IgM B cells vary in their surface levels of IgD, with the major circulating population of IgMIgD cells and a minor population (< 5%) of IgMIgD cells. In contrast, in gut-associated lymphoid tissue (GALT) derived from individuals undergoing tonsillectomy or appendectomy, IgMIgD B cells constitute ~ 30% of B cells. IgMIgD cells isolated from both tonsil and appendix lack plasma cell and B1 cell markers, and approximately 50% express the memory marker CD27. Functionally, GALT IgMIgD cells spontaneously secrete IgM, and class-switch to IgA in response to both T-dependent and T-independent stimulation ex-vivo. Immune repertoire profiling reveals that GALT IgMIgD cells exhibit lower levels of VH4-34 rearrangements, higher levels of somatic hypermutation, shorter CDR3 sequences and greater clonal overlap with switch memory cells than IgMIgD cells. Furthermore, clonal lineage analysis reveals that IgMIgD clones can include class-switched sequence variants. These findings suggest a maturational scheme starting from CD27IgMIgD B cells to CD27IgMIgD, and then to CD27IgMIgD, and finally to CD27IgMIgD B cells. In sum, IgMIgD B cells in the mucosa have memory features, give rise to class-switched memory B cells and antibody-secreting cells, and likely contribute significantly to the IgA repertoire in human GALT.
人类IgM B细胞表面IgD水平各异，主要循环群体为IgM IgD细胞，还有一小部分（<5%）为IgM IgD细胞。相比之下，在接受扁桃体切除术或阑尾切除术的个体的肠道相关淋巴组织（GALT）中，IgM IgD B细胞约占B细胞的30%。从扁桃体和阑尾分离出的IgM IgD细胞缺乏浆细胞和B1细胞标志物，约50%表达记忆标志物CD27。在功能上，GALT IgM IgD细胞可自发分泌IgM，并在体外对T细胞依赖性和T细胞非依赖性刺激作出反应时发生类别转换为IgA。免疫组库分析显示，与IgM IgD细胞相比，GALT IgM IgD细胞的VH4-34重排水平较低，体细胞高频突变水平较高，CDR3序列较短，与转换记忆细胞的克隆重叠更大。此外，克隆谱系分析表明，IgM IgD克隆可包括类别转换的序列变体。这些发现提示了一种成熟模式，即从CD27 IgM IgD B细胞开始，到CD27 IgM IgD，再到CD27 IgM IgD，最后到CD27 IgM IgD B细胞。总之，黏膜中的IgM IgD B细胞具有记忆特征，可产生类别转换的记忆B细胞和抗体分泌细胞，并可能对人类GALT中的IgA库有显著贡献。
