CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE : VI. CONTRIBUTION OF THYMUS-DERIVED CELLS AND ANTIBODY-FORMING CELL PRECURSORS TO IMMUNOLOGICAL MEMORY

Collaboration between thymus-derived lymphocytes and nonthymus-derived antibody-forming cell precursors occurs in the primary antibody response of mice to heterologous erythrocytes and serum proteins. The purpose of the experiments reported here was to determine whether collaboration took place in an adoptive secondary antibody response. A chimeric population of lymphocytes was produced by reconstituting neonatally thymectomized CBA mice soon after birth with (CBA x C57BL)F1 thymus lymphocytes. These mice could be effectively primed to fowl immunoglobulin G (FγG) and their thoracic duct lymphocytes adoptively transferred memory responses to irradiated mice. The activity of these cells was impaired markedly by preincubation with CBA anti-C57BL serum and to a lesser extent by anti-θ-serum. Reversal of this deficiency was obtained by adding T cells in the form of thoracic duct cells from normal CBA mice. Cells from FγG-primed mice were at least 10 times as effective as cells from normal mice or from CBA mice primed to horse erythrocytes. These results were considered to support the concept that memory resides in the T cell population and that collaboration between T and B cells is necessary for an optimal secondary antibody response. Poor antibody responses were obtained in irradiated mice given mixtures of thoracic duct cells from primed mice and of B cells from unprimed mice (in the form of spleen or thoracic duct cells from thymectomized donors). In contrast to the situation with T cells, the deficiency in the B cell population could not be reversed by adding B cells from unprimed mice. It was considered that memory resides in B cells as well as in T cells and that priming probably entails a change in the B cell population which is fundamentally different from that produced in the T cell population

EFFECT OF RECENT ANTIGEN PRIMING ON ADOPTIVE IMMUNE RESPONSES : I. SPECIFIC UNRESPONSIVENESS OF CELLS FROM LYMPHOID ORGANS OF MICE PRIMED WITH HETEROLOGOUS ERYTHROCYTES

When spleen, mesenteric lymph node, or Peyer's patch cells from mice primed 24 h before with either sheep erythrocytes (SRC) or horse erythrocytes (HRC) were transferred together with both SRC and HRC to irradiated mice, antibody responses measured 7 days later were very low to the priming antigen but high to the other antigen. This was demonstrated either by measuring numbers of antibody-forming cells in spleen or levels of hemagglutinins in serum. Specific unresponsiveness of the transferred cells was evident in both the 19S and 7S responses. It was observed only when strict experimental conditions were followed: (a) the cell donors had to be primed with not less than 109 erythrocytes given intravenously; (b) the cells had to be transferred between 1 and 2 days after antigen priming; (c) antibody responses in the recipients were measured within 7 days of cell transfer, i.e., partial recovery was evident by 11 days; (d) the transferred cells had to be challenged in the recipients within 1 day after cell transfer: when challenge was delayed for 5 days or longer, responsiveness returned. The failure of cells from recently primed donors to respond to the priming antigen on adoptive transfer could be overcome by supplementing with normal spleen cells, but not with thymus alone or bone marrow alone. This implied that unresponsiveness occurred at the levels of both T and B lymphocytes, and was not due to a suppressive influence exerted by T cells. Further work is in progress to determine the mechanism of this transient state of specific unresponsiveness

A RECEPTOR FOR ANTIBODY ON B LYMPHOCYTES : I. METHOD OF DETECTION AND FUNCTIONAL SIGNIFICANCE

Evidence is presented for the existence on all B lymphocytes, but not on T lymphocytes, of a membrane-associated receptor for antibody. The receptor was detected by a radioautographic technique in which lymphoid cells were incubated with antibody followed by the corresponding radioiodinated antigen. The ease with which antibody eluted during washing indicated that the bond between antibody and cell was weak. The formation of an antibody-antigen complex on the cell surface, however, stabilized the bond and permitted accurate quantitation of cells with adherent antibody. The ability of several combinations of antibody and antigen to adhere to the cells demonstrated the nonspecificity of the phenomenon and emphasized the need for care in interpretation of antigen-binding studies particularly when immune cells are being used. The identity of antibody-binding lymphocytes was established by two different approaches. In the first, mouse lymphocyte populations greatly enriched for either T cells or B cells were examined. Their T cell content was assessed by means of well-established markers such as the θ C3H isoantigen. When this was compared with the number of antibody-binding cells, an inverse relationship was obtained in each instance; thus almost all thoracic duct cells from athymic mice labeled with an immune complex although none were θ positive. The striking reduction in antibody-binding cells observed in bursectomized chickens provided a second and independent line of evidence suggesting that B cells, not T cells, bind antibody. The ability of B cells from primed animals to bind antibody in vivo made it important to test whether this phenomenon was related to the carriage of immunological memory. No correlation was, however, found between membrane-bound antibody and memory. It was proposed that the existence of a receptor of this kind may provide a rational explanation for antibody-dependent killing of target cells and may prove of importance in antigen concentration particularly during the secondary response

CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE : VIII. RADIOSENSITIVITY OF THYMUS-DERIVED LYMPHOCYTES

The helper function of carrier-primed T cells was found to be radiosensitive in vivo. The results could not be attributed to interference with the spleen-seeking properties of the irradiated cells. It is suggested that T cell division is essential for the induction of 7S antibody responses in vivo

CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE : VII. REQUIREMENT FOR DIFFERENTIATION OF THYMUS-DERIVED CELLS

Experiments were designed to test the possibility that thymus-derived (T) cells cooperate with nonthymus derived (B) cells in antibody responses by acting as passive carriers of antigen. Thoracic duct lymphocytes (TDL) from fowl γG-tolerant mice were incubated in vitro with fowl anti-mouse lymphocyte globulin (FALG), which was shown not to be immunosuppressive in mice. On transfer into adult thymectomized, irradiated, and marrow protected (TxBM) hosts together with a control antigen, horse RBC, a response to horse RBC but not to fowl γG was obtained. By contrast, TxBM recipients of nontolerant, FALG-coated TDL responded to both antigens and the antibody-forming cells were shown to be derived from the host, not from the injected TDL. These findings suggested that, under the conditions of the experiment, triggering of unprimed B cells in the spleens of TxBM hosts was not achieved with antigen-coated tolerant lymphocytes. Another model utilized the ability of B cells to bind antibody-antigen complexes. Spleen cells from TxBM mice, incubated in vitro with anti-fowl γG-fowl γG·NIP, were injected with or without normal TDL (a source of T cells) into irradiated hosts. Only mice given both cell types could produce an anti-NIP antibody response. In a further experiment, spleen cells from HGG·NIP-primed mice were injected together with NIP-coated B cells (prepared as above) into irradiated hosts. A substantial anti-NIP antibody response occurred. If, however, the T cells in the spleens of HGG·NIP-primed mice were eliminated by treatment with anti-θ serum and complement, the NIP response was abolished. It was concluded that antigen-coated B cells could not substitute for T cells either in the primary or secondary response. Treatment of T cells from unprimed or primed mice with mitomycin C impaired their capacity to collaborate with B cells on transfer into irradiated hosts. Taken together these findings suggest that before collaboration can take place T cells must be activated by antigen to differentiate and in so doing may produce some factor essential for triggering of B cells

Respiration and oxygen transport in soybean nodules

The respiration rate of individual soybean ( Glycine max Merr.) nodules was measured as a function of pO 2 and temperature. At 23°, as the pO 2 was increased from 0.1 to 0.9 atm, there was a linear increase in respiration rate. At 13°, similar results were obtained, except that there was an abrupt saturation of respiration at approximately 0.5 atm pO 2 . When measurements were made on the same nodule, the rate of increase in respiration with pO 2 was the same at 13° and 23°. Additional results were that 5% CO in the gas phase had no effect on respiration, except for a small decrease in the pO 2 at which respiration became saturated. Also, nodules still attached to the soybean root displayed the same respiratory behavior as detached nodules. A model for oxygen transport in the nodule is presented which explains these results quantitatively. The essence of the model is that the respiration rate of the central tissue of the nodule is almost entirely determined by the rate of oxygen diffusion to the respiratory enzymes. Evidence is given that the nodule cortex is the site of almost all of the resistance to oxygen diffusion within the nodule.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47460/1/425_2004_Article_BF00388605.pd