Kinetics of the reactive cell clones after immunosuppression and induction of tolerance. II. Different recovery of 19 S and 7 S plaque‐forming cells after induction of tolerance

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Abstract
By the aid of two alkylating agents (cyclophosphamide (CP) and 036.5122, (Asta), applied after a single dose of antigen, tolerance to sheep red blood cells (SRBC), has been induced in NMRI mice. Duration and characteristics of recovery were followed by a second antigenic challenge at various time intervals and by determination of 19 S and 7 S plaque-forming cells (PFC) 4 days later. During recovery from the tolerant state two phases of responsiveness could be differentiated: an early phase with no or markedly reduced numbers of total PFC, all of them being of the IgM type; a later phase with a steady increase in total PFC up to normal values, paralleled by an increase in the proportion of 7 S PFC finally reaching 90% of total PFC. In comparison with CP, recovery from tolerance induced by equitoxic doses of 5122 were delayed and modified. Even after 8 weeks, total PFC to SRBC were still depressed, and the ratio 19 S/7 S PFC resembled neither a typical primary nor secondary pattern. It is concluded that CP-mediated immunological tolerance is followed spontaneously by the establishment of a memory state. This observation, in agreement with findings of other authors, is interpreted as the expression of an established B cell memory compartment during the period of deficient T cell activity. The long-lasting modification of specific responsiveness after 5122 indicates a profound disturbance of the potency to recover from the impact of this alkylating agent, the biological base of which is as yet unidentified. It is suggested that observation of the characteristic features during the recovery phase from tolerance may help to clarify the nature of the defect in specific responsiveness.