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Summary Cellular events were followed during the latent and log phases of primary antibody response by culturing spleen cells in 0.1-µ diffusion chambers. The results show that the decrease in T2 of the total cells and the increase in the number of mitotic cells after antigenic stimulation are reflections mainly of proliferative activities of blast and plasma cells. Estimates of the ratio, S:GT, indicate that after antigenic stimulation a significant increase was detected only among the immature plasma cells and lymphocytes. This would indicate that either the S period is prolonged or the GT decreased. Of interest also was the fact that the ratio for the reticulum-blast cells was 0.9 (68/75). This would indicate that the G1 period of these cells is very short. These results indicate that one is confronted with at least three variables when he is dealing with an intermediate cell compartment of a differentiation process in an immune response, i.e., the variable cell cycle dependent upon the stimulant and the input and output rates. Taking into consideration the cell compartment size, the T2, T1/2, and S:GT of each cell compartment, we can conclude that the terminal plasma cells are the end state of differentiation of reticulum-blast cells, suggesting that if other unique somatic cells can give rise to terminal plasma cells they must do so by feeding into the primary cell compartment.

Summary The effect of antigen dose on adequately primed spleen cells was studied in cell-impermeable diffusion chambers. Maximum secondary antibody response against sheep red blood cells (RBC) was obtained when 1.2 × 107 spleen cells were cultured with 1.2 × 106 sheep RBC, a ratio of sheep RBC to spleen cells of 1:10. Maximum secondary antibody response against soluble bovine serum albumin (BSA) was obtained when 2.4 × 107 spleen cells were cultured with 50 µg of BSA. A suboptimum response was readily obtained not only by decreasing the antigen dose below the optimum but also by increasing it. Pulse-labeling studies with H3-thymidine were carried out during the log phase of response, when the total number of lymphoid cells remained relatively constant. The results revealed that antigenic stimulation can cause a twofold reduction in the t2 and therefore the t1/2 of the lymphoid cells from approximately 1.0 to 0.5 day. Further autoradiographic studies with use of H3-thymidine, H3-uridine and H3-proline revealed that morphologically distinct blast cells, lymphocytes and plasma cells are in general metabolically distinct, and the decrease in the t2 of the lymphoid cell population after antigenic stimulation is due to preferential proliferation of metabolically active blast cells and plasma cells. Furthermore they showed that the change in antibody output as affected by the dose of RBC antigen can be related mainly to the number of metabolically active plasma cells. Finally, immunofluorescent studies showed that when primed spleeen cells were cultured with over 100 times the optimum dose of BSA the number of functional antibody-forming cells decreased markedly 1 week after culture, and, in addition, the efficiency of these functional cells seemed to be reduced to one fourth of the normal. The significance of these results to the cytokinetics of antibody response is discussed.

Summary Labeled donor spleen cells colonized preferentially in the hematopoietic tissues of heavily irradiated, isologous recipient mice. More labeled cells were detected in the spleen and bone marrow than in the lymph node and thymus, and more were seen in the latter tissues than in the liver, lung, and small intestine. These results suggest that spleen cells have a “homing instinct” in irradiated recipients. Studies on the proliferative capacity of donor-labeled lymphoidal cells in the recipient spleen (H3T-Index and mean grain count/cell) indicate that the maximum mean generation time of these cells can be shortened 2-fold when stimulated by an antigen from ∼24 to ∼12 hr. This accelerated rate of proliferation occurs 2 days before the appearance of antibody in the circulation. The results, furthermore, suggest that mature plasma cells, following an antigenic stimulation, are derived from three to four cellular divisions.

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