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Cellular Bases for Relative Radioresistance of the Antibody-Forming System at Advanced Stages of the Secondary Response to Tetanus Toxoid in Mice¹

Department of Pathology, University of Bern, Switzerland, and the Medical Research Center, Brookhaven National Laboratory, Upton, New York 11973.

Abstract

Nearly normal secondary tetanus antitoxin responses were produced by young adult female mice subjected to 600 rads of ⁶⁰Co gamma whole-body radiation 4 days after secondary antigenic stimulation via the hind leg footpads. In an attempt to correlate the rapid transition from radiosensitivity of the antibody-forming system on day 3 to relative radioresistance on day 4 after booster, we carried out studies on cytokinetics in regional (popliteal) lymph nodes and on incorporation of ³H-l-histidine into circulating antitoxin. Analyses of tritium radioactivity in antigen-antibody precipitates of pooled sera 2 hr after i.v. injection of the labeled amino acid revealed maximum incorporation into antibody around day 7 after booster in nonirradiated controls, and around day 12, i.e., 8 days after radiation, in experimental mice, respectively. Relative radioresistance of the antibody-forming system on day 4 after booster, as opposed to day 3, was attributed to the finding that plasmacellular proliferation in medullary cords reached a marked and narrow peak on day 3 and had almost subsided to control levels between days 4 and 5. Accordingly, many medullary plasma cells survived and continued to proliferate after exposure to radiation. In contrast, germinal centers, which largely determine the overall maximum DNA synthetic activity in the lymph node and attain their full development in non-irradiated animals only 5 to 6 days after booster, were completely destroyed by radiation within 1 day. Since a) antibody production persisted despite the disappearance of germinal centers; and b) mice irradiated 4 days after booster have previously been shown to lack tertiary responsiveness, the present findings lend strong support to the hypothesis that germinal center cells were involved more in the generation of memory cells than in active antibody secretion. The results do not favor the assumption of a marked contribution of germinoblasts to the antibody-forming plasma cell population elicited by the same stimulus which had triggered germinal center formation.

Footnotes

¹ This work was supported by the Swiss National Foundation for Scientific Research and the United States Atomic Energy Commission.

² Present address: Department of Pathology, University of Bern, Freiburgstrasse 30, CH-3010 Bern, Switzerland.

³ Present address: Division of Microbiology, Medical Department, Brookhaven National Laboratory, Upton, Long Island, New York 11973.