Development of pre-B and B lymphocytes in the human fetus.

Cell suspensions from human fetal liver, bone marrow and spleen were systematically studied at between the fetal ages of 8 and 20 weeks by the direct immunofluorescence technique for the presence of pre-B and B cells. Pre-B cells were characterized as lymphoid cells containing cytoplasmic mu heavy chains but lacking surface IgM. Based on their size and morphological appearance, these cells were subdivided into large and small pre-B cells. In the livers of 8 week old fetuses, more than 90% of the total pre-B plus B cell population consisted of pre-B cells; the relative number of liver pre-B cells gradually decreased with increasing gestational age and, after the 14th week, B cells outnumbered pre-B cells. At 20 weeks, the ratio of pre-B to B cells was only 0.25. In contrast, the number of pre-B cells in fetal bone marrow (12-20 weeks) was always greater than that of the B cells. Large and small pre-B cells were present in the liver and bone marrow. Small pre-B cells outnumbered the large ones in both organs and with increasing gestational age the ratio of small to large pre-B cells increased four-fold. In fetal spleen (12-20 weeks), no large pre-B cells were seen and the small ones comprised only a minor fraction of the total B-cell population. It can be concluded from these data that during early human fetal life the liver is an important site of pre-B cell production. From 12 weeks onwards, this function is gradually taken over by the bone marrow. During the second half of pregnancy, pre-B cell production in fetal liver becomes very much less as compared with the bone marrow. No generation of pre-B cells takes place in the fetal spleen, but a certain amount of maturation of cells of the B cell line may take place in this organ.