The ontogeny of the functional capacity of B lymphocytes to generate a heterogeneous response to a haptenic determinant was studied by cell transfer techniques in LAF1 mice. Fetal liver, as a source of B lymphocytes, was transferred into adult, syngeneic, irradiated animals. All recipients received excess adult thymus cells so that T-cell activity did not limit the response and were immunized with DNP-BGG. The heterogeneity of avidity of their anti-DNP PFC response was assayed by hapten inhibition of plaque formation. Animals reconstituted with B lymphocytes from fetal donors produced a response that is highly restricted with respect to heterogeneity of affinity. Transfer studies using multiple fetal donors or mixtures of adult and neonatal cells for reconstitution suggest that the restriction in heterogeneity is not the consequence of suppressor T-lymphocyte activity. With animals reconstituted with B cells from day 16 or older fetal donors, injection of LPS together with antigen converted the response to a heterogeneous "adult-type" response. With animals reconstituted with B lymphocytes from day 14 fetal liver DxSO4, but not LPS, could convert the response to a highly heterogeneous one. Animals reconstituted with day 14 or 16 fetal liver as source of B lymphocytes were capable of producing a heterogeneous secondary response despite the fact that their primary response was of restricted heterogeneity. This implies the selection of high affinity B-memory cells, in the absence of high affinity PFC during the primary response with fetal B lymphocytes. Animals reconstituted with day 14 or 16 fetal liver produce only direct PFC, while animals reconstituted with day 18 fetal liver produce both direct and indirect PFC. Three differentiation events have therefore been defined in the functional development of B lymphocytes: (a) between day 14 and day 16 of fetal life they acquire responsiveness to LPS; (B) BETWEEN DAY 16 AND 18 OF FETAL DEVELOPMENT THEY ACQUire the capacity to produce indirect PFC; (C) between day 7 and 10 after birth they acquire the capacity to give a heterogeneous response after normal immunization. In addition, it was shown that LAF1 mice already have all of the information required to produce an "adult-type" heterogeneous anti-DNP response at day 14 of fetal life.

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