B-cell Immune Repertoire Sequencing in Tobacco Cigarette Smoking, Vaping, and Chronic Obstructive Pulmonary Disease in the COPDGene Cohort

Authors

Matthew Moll
Zhonghui Xu
Adel Boueiz
Min Hyung Ryu
Edwin K Silverman
Michael H Cho
Craig P Hersh
Maor Sauler
Francesca Polverino
Gregory L Kinney
Jeffrey L Curtis
Laura E Crotty-Alexander
Christopher Vollmers
Peter J Castaldi

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2025.1508786

PMID

40386772

PMCID

PMC12082042

PubMedCentral® Posted Date

5-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Rationale: 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.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Humans, Vaping, Male, Pulmonary Disease, Chronic Obstructive, Female, B-Lymphocytes, Middle Aged, Receptors, Antigen, B-Cell, Cigarette Smoking, Aged, Cohort Studies, Immunoglobulin Heavy Chains, Adult, COPD, B cell, immune repertoire, vaping, smoking

Published Open-Access

yes

Recommended Citation

Moll, Matthew; Xu, Zhonghui; Boueiz, Adel; et al., "B-cell Immune Repertoire Sequencing in Tobacco Cigarette Smoking, Vaping, and Chronic Obstructive Pulmonary Disease in the COPDGene Cohort" (2025). Faculty and Staff Publications. 4802.
https://digitalcommons.library.tmc.edu/baylor_docs/4802