ENHANCEMENT OF ANTIBODY FORMATION BY WHOLE-BODY X RADIATION
Studies were undertaken to elucidate mechanisms by which large doses of whole-body x radiation might enhance antibody formation. The effects of x rays on responses to a variety of antigens were studied in attempts to correlate the time of effectiveness of x rays with events transpiring in the immune response. It was found that not all antibody responses are equally enhanced by x radiation and that the time after antigen administration at which radiation has its greatest enhancing effect varies with the kind and the physical state of the antigen. In general, the most effective time of administration of x rays appears to be related to the beginning of cellular proliferation, detectable antibody formation, and the fixation of circulating antigens in the tissues. It was shown that whole-body x radiation in heavy, cytotoxic doses can increase and even accelerate the antibody response, particularly in primary responses to bovine gamma -globulin (BGG) (native and heat-aggregated) and hemocyanin, and to bovine serum albumin (BSA) when given after passively administered anti-BSA. The radiation must follow the antigenic stimulus, and the optimum time varies with the kind and form of the antigen. The more rapid the antibody response, the earlier x radiation may be given to enhance the response. With native BGG the interval between stimulus and max serum antibody was 10 to 11 days and x radiation gave max enhancement when administered 2 1/2 days after antigen. With heat-aggregated BGG the interval between stimulation and max antibody was only 7 to 8 days and x radiation gave max enhancement when administered as soon as 2 hr after antigen, although comparable enhancement also could be elicited with x rays 1 and 2 days after aggregated BGG. The long period during which x ray could be administered and still enhance the response to aggregated BGG may be related to the lack of uniformity in the size and therefore the behavior of the aggregates. Some were very large and were promptly removed from the circulation and others were small and persisted in the circulation. The proposed explanation of the radiation-induced enhancement of antibody formation is as follows: (a) x radiation given early in the immune response, probably before most of the cellular muitiplication has occurred, destroys the majority of lymphoid cells, leaving behind depleted lymphoid tissues. (b) of the remaining lymphoid cells, those that are responding would be expected to multiply much more rapidly than those that are unaffected by the antigen. (c) The cellular proliferative response after antigenic stimulation and x radiation together is more rapid and extensive than after either alone. During this exaggerated proliferation the rapidly dividing antigen-stimulated cells outgrow their nonstimulated counterparts, resulting in the observed increased antibody formation and large numbers of antibody-containing cells. A thymectomy experiment showed that the thymus does not play a major role in the immediate postradiation recovery of the antigen-stimulated lymphold tissues in contrast to its reported role in long-term postirradiation recovery. The enhancement of antibody formation by x rays is a convenient laboratory tool for obtaining hyperimmunized animals in a short period of time with little antigenic exposure. Also, these results contraindicate clinical attempts to inhibit by x radiation the immune response of patients to antigens recently administered, such as is used to delay or obliterate the homograft response of patients subjected to homografts. (H.H.D.)
- Research Organization:
- Scripps Clinic and Research Foundation, La Jolla, Calif.
- NSA Number:
- NSA-17-027121
- OSTI ID:
- 4689367
- Journal Information:
- J. Exptl. Med., Journal Name: J. Exptl. Med. Vol. Vol: 117
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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