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Some Aspects of Humoral Immunity in Germ-free and Conventional SJL/J Mice in Relation to Age and Pathology¹

Creighton University School of Medicine, Omaha, Nebraska 68178 [K. S.]; Lobund Laboratory, University of Notre Dame, Notre Dame, Indiana 46556 [M. P.]; and National Institute of Child Health and Human Development, Gerontology Research Center, Baltimore City Hospitals, Baltimore, Maryland 21224 [A. N.]

In this study the humoral immune competence of 130 germ-free and 137 conventional SJL/J mice was evaluated with increasing age. This evaluation was accomplished by means of the hemolytic plaque assay, in which spleen cells from 2- to 14-month-old animals were used to determine the presence of specific IgM and ₁ antibody-forming cells on Days 4, 5, and 6 after i.p. immunization with sheep erythrocytes. All animals were autopsied; spleen weights and total and differential peripheral blood leukocyte counts were recorded, and selected tissues were processed for histological study by light microscopy. Total protein estimates and -globulin comparisons, by means of acrylamide gel electrophoresis, were made on serum samples from selected animal groups.

The results show a similar plaque response between germ-free and conventional animals at all levels, as reflected in their ability to form specific antibody against sheep erythrocytes. The peak response for both IgM and ₁ production occurred at age 4 months with a subsequent progressive, marked, age-related decline. However, the age-associated depression was not consistent; most of the 10- to 14-month-old animals showed a severely depressed response, but a few aged animals responded at a level comparable to that of the 4-month-old group. The ₁ response was more severely impaired with age than the IgM response; however, the latter response showed a delay of 1 day in the peak of the response with aging. Animals with the lowest plaque-forming cell responses had high spleen weights and the most severe histological lesions of any of the groups studied. Animals with lymphoreticular lesions characterized by a predominance of reticulum cells, by a depletion of small lymphocytes and plasma cells, and by the presence of significant areas of fibrosis and cellular depletion had low or negative plaque-forming cell responses and low levels of -globulin. Animals with plasmacytic or lymphocytic hyperplasia had consistently high globulin levels but an unpredictable plaque-forming cell response. The peripheral blood total leukocyte and lymphocyte counts decreased significantly with age and progress of the disease.

These results found in the germ-free and in conventional SJL/J mice indicate that these animals have humoral immune dysfunction both as a predisposition and as a sequela to their characteristic lymphoreticular neoplasia.

¹ This work was supported in part by NIH Grant RR002924 and Sigma Delta Epsilon Grant-in-Aid.

² This work is based on a dissertation submitted in partial fulfillment of the requirements for the Ph.D. degree at the University of Notre Dame.

³ To whom reprint requests should be addressed, at Lobund Laboratory, University of Notre Dame, Notre Dame, Ind. 46556.

Received 7/20/73. Accepted 4/ 8/74.