Moll Matthew, Xu Zhonghui, Boueiz Adel, Ryu Min Hyung, Silverman Edwin K, Cho Michael H, Hersh Craig P, Sauler Maor, Polverino Francesca, Kinney Gregory L, Curtis Jeffrey L, Crotty-Alexander Laura E, Vollmers Christopher, Castaldi Peter J
Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, United States.
Front Immunol. 2025 May 2;16:1508786. doi: 10.3389/fimmu.2025.1508786. eCollection 2025.
Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.
To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.
BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at 5% FDR and suggestive associations at 10% FDR.
Among 234 non-Hispanic white (NHW) and African American (AA) participants, CS and dual-use were significantly positively associated with increased secretory IgA production, with dual-use showing the strongest associations. Dual-use was positively associated with class switching and B-cell clonal expansion, indicating increased B-cell activation, with similar trends in those only smoking or only vaping. The IGHV5-51*01 allele was increased in dual users.
CS and vaping additively enhance B-cell activation, most notably in dual-users. CS and vaping are significantly associated to multiple alterations in B-cell function including increased class switching, clonal expansion, and a shift towards IgA-producing cell populations. These changes could be relevant to response to infection and vaccinations and merit further study.
吸烟会损害B细胞功能和抗体产生，增加感染风险。使用电子烟（“吸电子烟”）以及同时吸烟和吸电子烟（“双重使用”）对B细胞活性的影响尚不清楚。
研究与吸烟、吸电子烟和双重使用相关的B细胞受体测序（BCR-seq）图谱。
对慢性阻塞性肺疾病基因（COPDGene）研究中234名参与者的血液RNA样本进行BCR-seq。我们评估了B细胞功能指标（免疫球蛋白重链（IGH）亚类表达和使用、类别转换、V等位基因使用和克隆扩增）与吸烟、吸电子烟和双重使用之间的多变量关联。我们使用Benjamini-Hochberg方法对多重比较进行校正，确定5%错误发现率（FDR）下的显著关联和10%FDR下的提示性关联。
在234名非西班牙裔白人（NHW）和非裔美国人（AA）参与者中，吸烟和双重使用与分泌型IgA产生增加显著正相关，双重使用显示出最强的关联。双重使用与类别转换和B细胞克隆扩增正相关，表明B细胞活化增加，仅吸烟或仅吸电子烟的参与者也有类似趋势。双重使用者中IGHV5-51*01等位基因增加。
吸烟和吸电子烟会累加增强B细胞活化，在双重使用者中最为明显。吸烟和吸电子烟与B细胞功能的多种改变显著相关，包括类别转换增加、克隆扩增以及向产生IgA的细胞群体转变。这些变化可能与对感染和疫苗接种的反应有关，值得进一步研究。
