Effects of In Utero Alcohol Exposure on B-Cell Development in the Murine Fetal Liver

Authors

  • Kristen L. Biber,

    1. Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreve-port, Louisiana.
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  • Kim M. Moscatello,

    1. Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreve-port, Louisiana.
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  • Deborah C. Dempsey,

    1. Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreve-port, Louisiana.
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  • Robert Chervenak,

    1. Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreve-port, Louisiana.
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  • R. Michael Wolcott

    Corresponding author
    1. Department of Microbiology and Immunology and the Biomedical Research Institute, Louisiana State University Medical Center, Shreve-port, Louisiana.
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  • This research was supported in part by the National Institute on Alcohol Abuse and Alcoholism (Grant AA09876) and by finds provided through the Center for Excellence in Cancer Research and Education, and the Center for Excellence in Arthritis and Rheumatology, Louisiana State University Medical Center. Additional support was provided to K.L.B. and K.M.M. through National Research Service Award Fellowships (Grants AA5441 and AA05427, respectively) awarded by the National Institute on Alcohol Abuse and Alcoholism.

Reprint requests: R. Michael Wolcott, Ph.D., Department of Microbiology and Immunology, Louisiana State University Medical Center, 1501 Kings Highway, Shreveport, LA 71130.

Abstract

Fetal alcohol syndrome is one of the leading causes of birth defects in this country. Children exposed to alcohol in utero suffer from growth and mental retardation, physical abnormalities, and immune dysfunction. Previous work from this laboratory demonstrated that B lymphopoiesis is delayed in mice exposed to alcohol in utero. The deficit in B-cell development was apparent shortly after birth and extended to well after weaning. Because lymphopoiesis begins in the fetal liver, the current study was done to determine if fetal B-cell development was affected as well by in utero exposure to alcohol. We now show that the effects of in utero alcohol exposure on B lymphopoiesis do not become apparent until late in gestation. Flow cytometry was used to enumerate several intermediates in the B-cell developmental pathway. These phenotypic analyses showed that before day 17 of gestation, B-lineage intermediates developed normally when compared with control animals. However, between days 17 and 18 of gestation, an abnormality in the population dynamics of B-lineage intermediates became apparent in the fetal liver of alcohol-exposed mice. Early intermediates in the B-cell developmental pathway were present in normal numbers; however, the more mature progenitors as well as B cells were decreased in number by gestational day 18. These data suggest that in utero alcohol exposure disrupts the ability of B-lineage intermediates to progress along the developmental pathway to maturity, thereby leaving the animal immunocompromised at birth.

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