Studies on immunological paralysis VII. Rapid reversal of Felton’s paralysis as evidence for ‘tolerant’ cells

CBA mice paralysed with 500 μg of S III showed an evanescent immune response on day 3 followed by PFC suppression in the spleen (1 order below background) up to 150 days. They remained totally refractory to S III immunization, but reacted normally to other antigens tested. Their spleen cells showed rapid escape from paralysis on transfer into 900 R-irradiated recipients. Increasing PFC levels were elicited by 5 μg S III up to 3 days later and lesser responses also developed without rechallenge. Emergent S III reactivity never equalled in amplitude that conferred by normal cells, diminished between 10 and 25 days of paralysis, but increased again after 50 and 88 days. PFC neutralization characteristics indicated that antibody of normal avidity was secreted. Increasing the S III dose to 2.5 mg produced total PFC suppression in the donors, but this paralysis was no more irreversible on transfer than that following 500 μg . ‘Paralysed’ bone marrow behaved similarly, except that it conferred responsiveness to S III after 7 days which was 3 times greater than that of normal cells. Rapid escape from S III paralysis cannot be explained by recruitment of fresh reactive cells from precursors. The full differentiation or antibody-synthesizing activity of S III-triggered B lymphocytes must, in some way, be reversibly blocked by the continuing presence of recirculating polysaccharide. Although such cells may be gradually eliminated and replaced, they fulfil the requirements of ‘tolerant’ cells.