A developmental switch occurs in B lymphopoiesis during the ontogeny of the mammalian immune system. Committed progenitor B cells present in fetal liver, but not adult bone marrow, differentiate exclusively into B cells bearing the phenotype IgM+ IgDlow CD5+ (B-1). B-1 cells differ from conventional IgMlow IgC+ CD5+-(B-2) cells in a number of ways. These include anatomic location in the body, self renewal capacity, early appearance in ontogeny and immunoglobulin gene expression. Antibodies produced by activated B-1 cells are generally polyreactive, exhibiting a low level of affinity for a variety of polysaccharide, lipid and protein antigens. Natural autoreactive antibodies are also products of B-1 cells. The object of this pilot project is to question whether the developmental switch which occurs in B-lymphopoiesis is caused by the transition which occurs at birth from a fetal to a neonatal endocrine environment. We have hypothesized that the maternal changes in B- lymphopoiesis (depression in B-2 cell generation) is serving as an indicator that the unique endocrine environment of pregnancy may facilitate stem cell pro-B-1 cell differentiation processes. The hypothesis that pro-B-1 cell differentiation takes place in the bone marrow of adult female mice during pregnancy will be tested using purified stem cell, committed pro B cell and bulk cell transfer experiments into lethally irradiated and SCID mice.
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