Pacheco Gaspar A, Rao Vishal, Yoo Duck Kyun, Saghaei Shahab, Tong Pei, Kumar Sachin, Marini-Rapoport Orlee, Allahyari Zahra, Moghaddam Ali S, Esbati Romina, Alirezaee Aida, Parnes Aric, Patil Sarita U, Wesemann Duane R
Department of Medicine, Division of Allergy and Clinical Immunology, Division of Genetics, Brigham and Women's Hospital; Boston, MA 02115, USA.
Harvard Medical School; Boston, MA 02115, USA.
bioRxiv. 2024 May 10:2024.05.08.592267. doi: 10.1101/2024.05.08.592267.
Bone marrow plasma cells (BMPCs) produce durable, protective IgM, IgG, and IgA antibodies, and in some cases, pro-allergic IgE antibodies, but their properties and sources are unclear. We charted single BMPC transcriptional and clonal heterogeneity in food-allergic and non-allergic individuals across CD19 protein expression given its inverse correlation to BMPC longevity. Transcriptional and clonal diversity revealed distinct functional profiles. Additionally, distribution of somatic hypermutation and intraclonal antibody sequence variance suggest that CD19low and CD19high BMPCs arise from recalled memory and germinal center B cells, respectively. Most IgE BMPCs were from peanut-allergic individuals; two out of 32 from independent donors bound peanut antigens in vitro and in vivo. These findings shed light on BMPC origins and highlight the bone marrow as a source of pathogenic IgE in peanut allergy.
骨髓浆细胞（BMPC）可产生持久的保护性IgM、IgG和IgA抗体，在某些情况下还会产生促过敏的IgE抗体，但其特性和来源尚不清楚。鉴于CD19蛋白表达与BMPC寿命呈负相关，我们绘制了食物过敏和非过敏个体中单个BMPC的转录和克隆异质性。转录和克隆多样性揭示了不同的功能谱。此外，体细胞超突变和克隆内抗体序列变异的分布表明，CD19低和CD19高的BMPC分别来自记忆B细胞和生发中心B细胞。大多数IgE BMPC来自花生过敏个体；32名独立供体中有两名在体外和体内都能与花生抗原结合。这些发现揭示了BMPC的起源，并突出了骨髓作为花生过敏中致病性IgE来源的作用。
