, Volume 62, Issue 4, pp 237–251 | Cite as

Impact of female cigarette smoking on circulating B cells in vivo: the suppressed ICOSLG, TCF3, and VCAM1 gene functional network may inhibit normal cell function

  • Feng Pan
  • Tie-Lin Yang
  • Xiang-Ding Chen
  • Yuan Chen
  • Ge Gao
  • Yao-Zhong Liu
  • Yu-Fang Pei
  • Bao-Yong Sha
  • Yan Jiang
  • Chao Xu
  • Robert R. Recker
  • Hong-Wen Deng
Original Paper


As pivotal immune guardians, B cells were found to be directly associated with the onset and development of many smoking-induced diseases. However, the in vivo molecular response of B cells underlying the female cigarette smoking remains unknown. Using the genome-wide Affymetrix HG-133A GeneChip® microarray, we firstly compared the gene expression profiles of peripheral circulating B cells between 39 smoking and 40 non-smoking healthy US white women. A total of 125 differential expressed genes were identified in our study, and 75.2% of them were down-regulated in smokers. We further obtained genotypes of 702 single nucleotide polymorphisms in those promising genes and assessed their associations with smoking status. Using a novel multicriteria evaluation model integrating information from microarray and the association studies, several genes were further revealed to play important roles in the response of smoking, including ICOSLG (CD275, inducible T-cell co-stimulator ligand), TCF3 (E2A immunoglobulin enhancer binding factors E12/E47), VCAM1 (CD106, vascular cell adhesion molecule 1), CCR1 (CD191, chemokine C-C motif receptor 1) and IL13 (interleukin 13). The differential expression of ICOSLG (p = 0.0130) and TCF3 (p = 0.0125) genes between the two groups were confirmed by real-time reverse transcription PCR experiment. Our findings support the functional importance of the identified genes in response to the smoking stimulus. This is the first in vivo genome-wide expression study on B cells at today’s context of high prevalence rate of smoking for women. Our results highlight the potential usage of integrated analyses for unveiling the novel pathogenesis mechanism and emphasized the significance of B cells in the etiology of smoking-induced disease.


Cigarette smoking B cells Microarray Genome-wide Association 



We thank Dr. Peng Xiao for coordinating the RT-PCR experiment. This work was partially supported by the LB595 and LB692 grant from the State of Nebraska. The study was also benefited from support from Xi’an Jiaotong University, Shanghai Leading Academic Discipline Project (project number S30501) and the Ministry of Education of China. HWD was partially supported by grants from NIH (P50AR055081, R01AG026564, R01AR050496, RC2DE020756, R01AR057049, and R03TW008221) and Franklin D. Dickson/Missouri Endowment.

Supplementary material

251_2010_431_MOESM1_ESM.doc (320 kb)
Appendix 1(DOC 320 kb)
251_2010_431_MOESM2_ESM.doc (74 kb)
Appendix 2(DOC 73 kb)


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Feng Pan
    • 1
    • 2
  • Tie-Lin Yang
    • 1
    • 3
  • Xiang-Ding Chen
    • 2
    • 4
  • Yuan Chen
    • 1
    • 2
  • Ge Gao
    • 2
  • Yao-Zhong Liu
    • 3
  • Yu-Fang Pei
    • 1
    • 3
  • Bao-Yong Sha
    • 1
    • 2
  • Yan Jiang
    • 5
  • Chao Xu
    • 5
  • Robert R. Recker
    • 2
  • Hong-Wen Deng
    • 1
    • 3
    • 4
    • 6
  1. 1.The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and TechnologyXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Department of Biomedical Sciences and Osteoporosis Research Center, School of MedicineCreighton UniversityOmahaUSA
  3. 3.Departments of Orthopedic Surgery and Basic Medical Science, School of MedicineUniversity of Missouri-Kansas CityKansas CityUSA
  4. 4.Laboratory of Molecular and Statistical GeneticsCollege of Life Sciences Hunan Normal UniversityChangshaPeople’s Republic of China
  5. 5.Institute of Systems Science, School of ManagementUniversity of Shanghai for Science and TechnologyShanghaiPeople’s Republic of China
  6. 6.Center of Systematic Biomedical ResearchUniversity of Shanghai for Science and TechnologyShanghaiPeople’s Republic of China

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