Murine embryonic B lymphocyte development in the placenta

Abstract

B LYMPHOCYTES derive from pluripotent stem cells which give rise to erythrocytes, granulocytes, monocytes, macrophages and T and B lymphocytes^1,2. Stem cells have been found in yolk sac, fetal liver, bone marrow, spleen and blood. During ontogeny from stem cells to mature B cells, precursor B cells (pre-B cells) can be found. Various types of pre-B cell can be identified. There are those which already produce and release immunoglobulin (Ig), but which are morphologically different from mature B cells^3,4. Using surface-bound Ig as a marker for the development of mature B cells, it has previously been found that fetal liver, but not yolk sac, could develop mature B cells in vitro^5,6. A second type of pre-B cell can be characterised functionally as not being reactive to antigen or mitogens but which, on adoptive transfer into irradiated recipients or following in vitro culture, develops into a reactive cell^7–9. When stimulated by antigens or mitogens, such mature, reactive surface Ig-bearing resting B lymphocytes develop into IgM-, IgG- and IgA-secreting plasma cells, which can be detected using a haemolytic plaque assay as plaque-forming cells (PFC)^10,11. Pre-B cells which develop into antigen- or mitogen-reactive cells have been localised in fetal liver, bone marrow and spleen. The earliest that pre-B cells had previously been identified during embryogenesis of the mouse was at about day 12 or 13, but I report here the detection of IgM- and IgG-secreting PFC in mitogen-stimulated cultures of single cell suspensions of mouse placenta 9–14 d old. Placenta is thus identified as a new site of B-lymphocyte development which, during embryogenesis, precedes B-cell generation in fetal liver.