The Journal of Experimental Medicine
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The Journal of Experimental Medicine, Vol 133, 973-986, Copyright © 1971 by The Rockefeller University Press

ARTICLE

ANTIGEN-SPECIFIC CELLS IN MOUSE BONE MARROW : II. FLUCTUATION OF THE NUMBER AND POTENTIAL OF IMMUNOCYTE PRECURSORS AFTER IMMUNIZATION



Harold C. Miller Ph.D.1 and Gustavo Cudkowicz M.D.1

1 From the Department of Pathology, School of Medicine, State University of New York at Buffalo, Buffalo, New York 14214

Quantitative and qualitative changes of mouse bone marrow cells were studied by limiting dilution assays 2–3.5 months after immunization of donors with sheep erythrocytes or unrelated antigens (Salmonella typhimurium, horse and chicken erythrocytes). Irradiated (C3H x C57BL/10)F1 mice were reconstituted with an excess of nonprimed thymocytes and small graded numbers of primed bone marrow cells. Direct and indirect plaque-forming cells (PFC) were induced by secondary stimulation with SRBC and enumerated on the 9th day after cell transplantation.

Marrow precursors of PFC (P-PFC) cooperated with thymocytes in the production of direct and indirect PFC after SRBC priming. The limiting dilution plots, which were not compatible with predictions of the Poisson model before immunization, changed and conformed to this model afterwards, as if the population of P-PFC had become functionally more homogeneous. The concentration of marrow P-PFC increased up to the 3rd month after priming, and decreased during the 4th, varying over two logarithms of nucleated marrow cells. The fluctuation was simultaneous and of the same order of magnitude for precursors of direct and indirect PFC, which were class restricted. A third effect of immunization was detected at 3.5 months: individual precursor units generated 3–4 times more direct and indirect PFC than at earlier intervals. Qualitative and quantitative changes of marrow P-PFC participating in anti-sheep responses were specific, since antigens unrelated to SRBC failed to induce them. The data suggested that marrow-derived cells were the major carriers of immunologic memory, but that they functioned in cooperation with thymus-derived inducer cells during secondary anti-sheep responses.

 Submitted on December 20, 1970


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