Antibody Formation in Mouse Bone Marrow III. EFFECTS OF ROUTE OF PRIMING AND ANTIGEN DOSE.

The influence of the route of priming and the dose of sheep red blood cells (SRBC) on the IgM, IgG and IgA-plaque-forming cell (PFC) activity in mouse bone marrow during the secondary response to SRBC was studied. After intraperitoneal and subcutaneous priming the number of IgM, IgG and IgAPFC during the secondary response increased with the number of SRBC used for priming. After intravenous (i.v.) priming the priming dose—secondary response relationship was found to be an optimum curve for IgM-PFC as well as for IgGand IgA-PFC. A peak secondary response in the bone marrow was found after priming with 10⁷ and with 10⁸ SRBC i.v. The appearance of IgG- and IgA-memory cells in the bone marrow after i.v. immunization with SRBC was shown to be dependent on the priming dose: the appearance of IgG-memory cells required a higher dose of SRBC than the appearance of IgM-memory cells, and the appearance of IgA-memory cells required even more antigen.The effect of the booster dose upon the PFC activity was studied in mice primed with 10⁷ SRBC i.v. and boosted with 10⁴, 10⁶, or 10⁹ SRBC i.v. 2 months later. IgM-PFC as well as IgG- and IgA-PFC were present in spleen and bone marrow at each booster dose tested. In each group of mice the PFC activity in the bone marrow rose to a level which surpassed the level in the other lymphoid organs between the 7th and 10th day after the booster injection. Thus, independently of the booster dose, mouse bone marrow is the major source of PFC during the late phase of the secondary response to SRBC. Mice boosted with 10⁹ SRBC i.v. showed a prolonged presence of IgM-, IgG- and IgA-PFC in the thymus. Light and electron microscopic studies revealed the presence of plasma cells and macrophages studded with phagocytosed material in the thymic medulla of these mice, thus providing evidence for a real PFC response within the thymus. A thymic PFC response was absent in mice boosted with either 10⁴ or 10⁶ SRBC i.v. Therefore the thymic PFC activity during the secondary response to SRBC does depend on the booster dose. [ABSTRACT FROM AUTHOR]