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The Absence of Antibody-Producing Cells during Unresponsiveness to BSA in the Mouse¹

From the Department of Bacteriology and Immunology, Harvard Medical School, Boston, Massachusetts

Abstract

Studies of experimentally induced immunologic unresponsiveness to bovine serum albumin were carried out in both newborn and adult mice with the following results:

1. No cells containing antibody were found in the spleen and lymph nodes of newborn mice injected daily from birth to adulthood within a 2000-fold range of bovine serum albumin (BSA) doses.

2. Mice injected from the 5th week of life to adulthood were rendered unresponsive by high doses of antigen but not by low ones.

3. Both the newborn and adult series of animals possessed circulating antigen, but no antibody or BSA-anti-BSA complexes could be demonstrated.

4. Paralysis was specific: these mice responded to diphtheria toxoid with the production of antitoxin detectable in the serum and in cells of the lymphoid tissue.

5. Transfer of cells of the unresponsive spleen and lymph nodes to a normal mouse, with or without antigenic stimulation of the recipient, did not result in antibody formation within 7 days, as it did with stimulated cells.

6. Recovery from unresponsiveness to BSA took place a few weeks after the level of circulating antigen became undetectable. No further antigenic challenge was required to induce the synthesis of antibody. Lengthening the period of antigen administration lengthened the subsequent period during which antigen was detected and antibody formation was inhibited.

These data lead to the following working hypothesis: "paralyzed" animals do not produce antibody but rather their cells are specifically inhibited; such an immunologically paralyzed cell is, however, a potentially stimulated cell when the concentration of antigen falls below an effective inhibitory level.

Footnotes

¹ This investigation was conducted in part under the sponsorship of the Commission on Immunization of the Armed Forces Epidemiological Board, and was supported in part by the Surgeon General, Department of the Army, and by United States Public Health Grant No. H-2255.

² Career Investigator, the American Heart Association.

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