EFFECTS OF IN-UTERO ALCOHOL EXPOSURE ON B-CELL DEVELOPMENT IN THE MURINE FETAL LIVER

Fetal alcohol syndrome is one of the leading causes of birth defects i n this country. Children exposed to alcohol in utero suffer from growt h and mental retardation, physical abnormalities, and immune dysfuncti on. Previous work from this laboratory demonstrated that B lymphopoies is Is delayed in mice exposed to alcohol in utero. The deficit in B-ce ll development was apparent shortly after birth and extended to well a fter weaning. Because lymphopoiesis begins in the fetal liver, the cur rent study was done to determine if fetal B-cell development was effec ted as well by in utero exposure to alcohol. We now show that the effe cts of in utero alcohol exposure on B lymphopoiesis do not become appa rent until later in gestation, Flow cytometry was used to enumerate se veral intermediates in the a-cell developmental pathway. These phenoty pic analyses showed that before day 17 of gestation, B-lineage interme diates 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 five r of alcohol-exposed mice. Early intermediates in the B-cell developme ntal pathway wets 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 th e ability of B-lineage intermediates to progress along the development al pathway to maturity, thereby leaving the animal immunocompromised a t birth.