It is proposed to study the ontogeny of the capacity of the B lymphocyte population to produce a heterogeneous (polyclonal) immune response. B cells from fetal or neonatal donors will be transferred into lethally irradiated adult recipients which also receive optimal numbers of adult thymus cells. Thus, the function of the immature B-cell population will be tested in an adult environment in the presence of adult thymus cells. Using this system it was shown that cells from fetal or neonatal donors produce a response of restricted clonality unless they are treated with a polyclonal B-cell activator under which circumstances they produce a fully heterogeneous, adult-type response. It is proposed to determine how early in development B cells are capable of producing such a fully heterogeneous response; that is, how early all genetic information is present. We have previously shown that the B-cell population acquires the capacity to generate a heterogeneous response (in the absence of a B-cell mitogen) between seven and ten days after birth. This maturational event will be studied to determine: (a) if it takes place at the same time with different antigens; (b) if it is under genetic control; (c) if the differentiation is controlled by an "internal cell clock" or is "environmentally" induced; d) if this maturational event is controlled by the thymus; e) if this differentiation event is associated with the appearance of other B lymphocyte markers. It will also be determined in the same cell transfer system if there is a change in the sensitivity of B cells to tolerance induction during the course of fetal or neonatal development.