The major goals are to define the defects in lymphocyte differentiation or function associated with immune deficiency diseases, lymphoid malignancies, and disorders of immunoregulation. The underlying thesis is that some of the gaps in knowledge about the human immune system can be addressed by the comparative analysis of the normal ontogeny of the immune system and the immune system defects in primary immunodeficiency diseases. Emphasis is on (1) the ontogeny of B cell development in humans, (2) the genetic basis of immunodeficiency, and (3) the influence of gene defects on the differentiation of immunocompetent cells. A major predictor of childhood atopy is the concentration of IgE in the cord blood, but whether the source of the IgE is maternal or fetal remains unclear. Through examination of fetal, neonatal, and infant samples; we sought to determine the developmental pattern of in situ IgE production during fetal and neonatal life. We found that B lymphocytes, especially from individuals with IL-4R A1902G allele, appear primed to undergo IgE class switching from the earliest stages of ontogeny and can produce IgE, but IgE producing cells are rare in the blood until nine months after birth.