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E A Goidl

Publications and source records attributed to E A Goidl.

47 records · Page 3Linked to original sources

Ontogeny of B-lymphocyte function with respect to the heterogeneity of antibody affinity-1,2.

Neonatal liver or adult spleen was used as a source of B-lymphocytes in reconstituting lethally irradiated, syngeneic mice. Recipients were all given excess adult, syngeneic thymus cells and were immunized with dinitrophenylated bovine gamma globulin. The distribution of avidities of plaque-forming cells produced by immunized recipients of neonatal liver was highly restricted in comparison with animals reconstituted with adult spleen indicating a restriction of B-lymphocyte heterogeneity in the neonatal mouse.

Animals↗

Studies on the control of antibody synthesis. VII. Change in affinity of direct and indirect plaque-forming cells with time after immunization in the mouse: loss of high affinity plaques late after immunization.

The change in avidity of anti-hapten antibody with time after immunization was studied in mice at the level of the antibody-forming cell. A progressive increase in avidity was seen in both direct and indirect plaque-forming cells. Late (38 days) after immunization with a large dose of antigen there was a preferential loss of high avidity plaque-forming cells and the average avidity decreased. High avidity memory cells were still present since boosting resulted in the prompt appearance of very high avidity plaque-forming cells. There was a strong positive correlation between the avidity of the direct and the indirect plaque-forming cells present in the same spleen. A pattern of change in avidity and heterogeneity of avidity similar to that observed with intact animals was seen in lethally irradiated mice reconstituted with normal spleen and thymus cells.

Animals↗

Ontogeny of B-lymphocyte function. I. Restricted heterogeneity of the antibody response of B lymphocytes from neonatal and fetal mice.

The ontogeny of the ability of B lymphocytes to produce an antihapten response which is heterogeneous with respect to affinity for the antigenic determinant was studied in a cell transfer system. The heterogeneity of affinity of the immune response of lethally irradiated mice reconstituted with syngeneic, adult thymus cells and fetal or neonatal tissues as a source of B lymphocytes was studied. It was found that B cells from 17 day fetal liver or neonatal liver are highly restricted with respect to heterogeneity of affinity as compared with adult spleen or bone marrow. The B-cell population achieves an adult character with respect to heterogeneity of affinity by 2 wk of age. The peripheral lymphoid tissues (spleen) appear to mature in this respect more rapidly than do central lymphoid tissues (bone marrow). Spleens from 10-day old donors behave in an adult, heterogeneous manner while bone marrow from the same donors exhibit a marked restriction in heterogeneity of affinity. Germfree mice produce an immune response which is indistinguishable from conventionally reared adult animals with respect to heterogeneity of affinity. The earlier appearance of the ability to transfer a heterogeneous immune response in spleen as compared with bone marrow suggests that the increasing heterogeneity of the B-lymphocyte population which occurs between birth and 2 wk of age is the result of a differentiation event and not of a somatic mutation or recombination event.

Animals↗

Inhibition of aggregation and differentiation of Dictyostelium discoideum by antibodies against adenosine 3':5'-cyclic monophosphate diesterase.

A specific antibody directed against adenosine 3':5'-cyclic monophosphate diesterase (c-AMP diesterase; EC 3.1.4.c), which is secreted by the amoeboid slime mold, Dictyostelium discoideum, was prepared in rabbits. Purified gammaglobulin fractions that contain the antibodies inhibited the activity of cAMP diesterase preparations in vitro and interfered with aggregation and development in vivo. While cells that were treated with antibody were unable to aggregate because of the inability to destroy cAMP, they aggregated normally when washed free of antibody.

Animals↗

Carrier function in anti-hapten antibody responses. 3. Stimulation of antibody synthesis and facilitation of hapten-specific secondary antibody responses by graft-versus-host reactions.

The studies reported here demonstrate that immunocompetent lymphoid cells from allogeneic donor guinea pigs stimulate the synthesis of anti-DNP and anti-OVA antibodies by recipients previously primed with DNP-OVA. This allogeneic effect occurs spontaneously in the absence of any further anti-genic challenge. Furthermore, the transfer of allogeneic cells prepares DNP-OVA-primed recipients for a striking secondary anti-DNP response to DNP-BGG; this occurs in equal degree whether or not the cells are derived from BGG-primed donors. We suggest that the allogeneic cells function by virtue of a specific immunologic attack of grafted cells on host cells. This conclusion is made on the basis of the following evidence: (a) The failure of observing the phenomenon with L(2)C leukemia cells and irradiated strain 2 lymph node and spleen cells which, although capable of initiating a host-versus-graft response, are incapable of mediating graft-versus-host reactions; and (b) the inability of (strain 2 x strain 13) F(1) hybrids to mediate the allogeneic effect in strain 13 recipients. The analysis of this phenomenon may offer a key to the delineation of mechanisms involved in the activation of precursors of antibody-forming cells.

Animals↗

Radioresistance of cooperative function of carrier-specific lymphocytes in antihapten antibody responses.

Transfer of lymphoid cells from strain-2 guinea pigs immunized to bovine gamma globulin into syngeneic recipients immunized with dinitrophenyl ovalbumin markedly enhances the secondary antidinitrophenyl response of the recipient to challenge with dinitrophenyl-bovine gamma globulin. This function of the carrier bovine gamma globulin-specific cells is resistant to irradiation with up to 5000 rads, although the capacity of the irradiated cell population to transfer immunologic memory for bovine gamma globulins or to be stimulated by antigen to synthesize DNA in vitro is abolished by this treatment.

Animals↗

Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization.

Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 microg of BGG is more effective than a dose of 50 microg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for epsilon-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.

Aminocaproates↗

Carrier function in anti-hapten immune responses. II. Specific properties of carrier cells capable of enhancing anti-hapten antibody responses.

Transfer of live lymphoid cells from BGG-immunized strain 2 guinea pigs into syngeneic animals primed with DNP-OVA prepares the recipients for a markedly enhanced secondary anti-DNP antibody response upon challenge with DNP-BGG. This phenomenon has been demonstrated when the recipients were challenged 1 day after cell transfer, but it was considerably more striking when an interval of 6 days was allowed between transfer of cells and challenge with antigen. As demonstrated in the preceding paper (6), BGG preimmunization enhanced anti-DNP antibody responses to challenge with DNP-BGG. An analysis of the characteristics of substances to which preimmunization was effective in enhancing subsequent anti-hapten responses was made. It was shown that preimmunization of strain 13 guinea pigs with a copolymer of glutamic acid and lysine (GL), to which these animals are genetically unable to accord an immune response, failed to prepare them for an enhanced anti-DNP response to DNP-GL. Tolerance to BGG specifically abrogated the capacity of subsequent BGG immunization to prepare DNP-OVA primed rabbits for an enhanced anti-DNP response to DNP-BGG. Sensitization of animals to haptens by preimmunization with hapten-protein conjugates failed to prepare them for enhanced primary or secondary antibody responses to other determinants associated with that hapten on a different carrier. These studies indicate that the enhancing effect of carrier preimmunization reflects a cooperative interaction between lymphoid cells specific for carrier and cells specialized for haptenic determinants. Furthermore, the capacity of a substance to behave as a carrier requires more than its possession of a variety of antigenic determinants.

Animals↗

On a model for ontogenic development.

A theory to explain both the endogenous control of differentiation and programmed organismal aging as the result of one fundamental regulatory mechanism is advanced. It is postulated that these phenomena are linked to cell division, which is presumed to be the primary unit of measurement for the organism's maturation and aging. The hypothesis developed here holds that a genetic locus (DSI), modulating both cell division and enzyme induction, is first activated and then inactivated with each cycle. The number of DSIs in the genome of each cell is finite, cellular sensescence occurring when the genome is depleted of functional DSIs. Protein inducers are linked to specific DSIs, which are only transcribed at appropriate times during ontogeny, this in turn being a function of the number of DSIs previously inactivated during earlier mitoses. Experimental approaches which could test this model are discussed.

B-Lymphocytes↗