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J W Goodman

Publications and source records attributed to J W Goodman.

At least 55 records · Page 3Linked to original sources
PubMed1978

Dose-dependence of the augmentation of hemopoiesis by thymocytes.

We have used the spleen colony assay and the 24-h uptake of 59Fe by hemopoietic tissues to study certain quantitative aspects of the interaction of parent-strain thymocytes and marrow cells transplanted into lethally irradiated F1 hybrid mice. The data show that thymocytes augment bone marrow growth at least partly by increasing the proportion of stem cells from parental marrow that from colonies in the hybrid animal. This increase in spleen colony number is a linear function of the number of thymocytes injected within certain dose ranges. At higher thymocytes doses, a plateau is reached where further increase in the number of thymocytes injected does not result in an increase in the number of spleen colonies; this plateau occurs at just that level of response given by the same marrow dose when transplanted into isogeneic (parent-strain) recipients. Experiments in which 59Fe uptake up red blood cells and spleen was used to measure marrow growth yielded similar results, except that the plateau in uptake occurred at a much lower level than that measured for the same marrow dose in isogeneic recipients. This apparent discrepancy in results obtained from the two different assays may best be explained by the recent observation that thymocytes shift the differentiation pattern of marrow stem cells away from erythropoiesis and toward granulopoiesis. The absolute thymocyte dose seems to be more important than the thymocyte: marrow-cell ratio in determining the degree of augmentation observed.

Animals↗
PubMed1978

Colony-forming units in the spleen and bone marrow of young (C57BL/6xDBA/2)F1 hybrid mice.

Spleen or bone marrow cells from (C57BL/6 X DBA/2)F1 hybrid mice ranging in age from 1 to 32 days were transplanted into syngeneic irradiated adult recipients. By enumeration of macroscopic hemopoietic spleen colonies 8 days after transplantation, the colony-forming unit(CFU) content of the spleen and bone marrow of the young donor mice was determined. The CFU concentration in the bone marrow, initially at a level of 15.1--17.0 CFU/105 nucleated cells, increased during the third week of life and reached a value comparable to that of the adult during week 4. In contrast, the CFU concentration of the spleen decreased during the first 2 weeks and reached a plateau at a level of 4.45--6.66 CFU/105 nucleated cells during the third and fourth weeks of age. This was still significantly higher than that of the adult hybrid. The rise in prominence of the bone marrow as a hemopoietic organ during this period appeared to be due to an increase in total cellularity coupled with an increase in CFU concentration in this hybrid. While the cellularity of the spleen also increased during this time, the CFU concentration decreased, resulting in little change in the total CFU content of this organ.

Animals↗
PubMed1978

On the role of thymus in hemopoietic differentiation.

This study was performed to investigate further the connection between the thymus and blood formation suggested by earlier findings. Bone marrow, after in vitro treatment with either anti-thy 1.2 (alpha Thy 1.2) or nonimmune serum and complement, was transplanted to two separate groups of lethally X-irradiated isogenic recipient mice of several different genotypes. Twelve studies were done, and macroscopic spleen-colony numbers were found to be similar in the two groups; however, differences were found when spleens were examined microscopically. The most striking and consistent finding was a decrease in granulopoietic colonies in recipients of alpha-Thy-1.2-treated marrow. There were less pronounced decreases in erythropoietic and in total colonies (all hemopoietic kinds). Ratios of erythropoietic to granulopoietic colonies were regularly increased. Anemia did not develop over a period of 4 months in chimeras given either kind of treated marrow.

Animals↗
PubMed1977

Carrier-directed anti-hapten responses by B-cell subsets.

The capacity of the trinitrophenyl (TNP) haptenic group, coupled to a series of chemically dissimilar carriers, to cross-stimulate putative T- dependent and T-independent murine B-cell subpepulations was determined by using an in vitro limiting dilution technique to generate primary IgM responses. It was found that TNP-Ficoll and TNP-dextran, two T- independent antigens with little or no polyclonal mitogenicity, stimulate the same population of anti-TNP precursors, which is distinct from the precursor population activated by TNP-bacterial lipopolysaccharide (LPS), a T-independent polyclonal mitogen, or TNP-horse erythrocytes (HRBC), a T-dependent antigen. On the other hand, TNP-LPS and TNP-HRBC activate the same precursor population, indicating that LPS can substitute for the T- cell signal in T-dependent B-cell responses, whereas nonmitogenic T- independent antigens cannot. However, the cumulative evidence from this and other laboratories strongly indicates that LPS and T-dependent antigens activate B cells by different mechanisms. Of particular interest, LPS is incapable of activating B cells responsive to weakly- or nonmitogenic T-independent antigens. Based on clonal burst size, T-dependent antigens are capable of inducing greater antigen-specific B-cell proliferation than T-independent antigens. However, TNP conjugates of Ficoll and dextran, which are relatively poor inducers of polyclonal B-cell activation, induced larger anti-TNP clones than did TNP-LPS, a strong polyclonal mitogen. The findings reinforce the evidence favoring existence of multiple B- cell subpopulations with distinctive activation pathways. They also strengthen the proposition that a given B-cell subset can be activated by more than one mechanism.

Animals↗
PubMed1977

Complement-dependent and -independent pathways of T cell-B cell cooperation.

BDF1 mice treated with CoV had markedly reduced levels (less than 20%) of native serum C3 32 hr later, whereas the frequency of splenic CR+ cells was normal. CoV treatment before immunization reduced the IgM PFC response to a T-dependent antigen (TNP-SRBC) by more than 60%. Inclusion of highly specific anti-C3 antibody had no effect on the T-dependent IgM response of CR- B cells. The residual PFC responses in cultures of unfractionated spleen cells treated with anti-C3 could be largely or completely accounted for by CR- B cells in the cultures. The effect of anti-C3 antibody was not due to cytotoxicity. These data collectively indicate that the effect of CoV on T-dependent antibody responses is due to decreased C3 in serum rather than to interaction of C receptors directly with CoV or with C3 cleavage products. They suggest the existence of at least two distinct pathways of T-B cooperation, one in which C3 is an obligatory participant and another in which it may be uninvolved.

Animals↗
PubMed1976

Murine B-cell subpopulations responsive to T-dependent and T-independent antigens.

Strain A/J mice made secondary indirect plaque-forming cell (PFC) responses to azobenzenearsonate (ABA) conjugates of giant keyhole limpet hemocyanin (KLH), a thymic-dependent antigen, but not to conjugates of Ficoll, a T-independent antigen. ABA-Ficoll was also unable to elicit a response in animals primed with ABA-KLH, which have an expanded anti-ABA memory cell pool. On the other hand, ABA-Ficoll rendered mice unresponsive to ABA-KLH when administered before priming or boosting with the T-dependent immunogen. Hence, the T-independent antigen was able to tolerize but unable to trigger B-memory cells responsive to the T-dependent antigen. A/J mice immunized with dinitrophenyl conjugates of Ficoll or bovine IgG (BGG) made vigorous IgM and IgG PFC responses. PFC responses to ABA-KLH and 2,4-dinitrophenyl (DNP)-BGG were abrogated by depleting mice of C3 with cobra venom factor, whereas the IgM and IgG PFC responses to DNP-Ficoll were unaffected. B lymphocytes were fractionated on the basis of receptors for C3 and the subpopulations were assayed for in vitro PFC responses to DNP-Ficoll. Very little response was obtained from complement receptor lymphocyte [CRL(+)] B cells, whereas CRL(-) cells were more responsive than unfractionated B cells. Both populations responded to a polyclonal B-cell mitogen (lipopolysaccharide). On the other hand, the in vitro PFC response to a T-dependent antigen (sheep erythrocytes) correlated with the presence of CRL(+) B cells in the cultures. However, a minor component of this response, sensitive to anti-Thy-1 serum, was made by CRL(-) B cells, indicating the existence of subpopulations of T-dependent B cells with different signalling requirements. The results suggest that most B cells responsive to T-dependent antigens possess receptors for C3 and that C3 plays an obligatory role in the response of these cells. A distinct subpopulation of B cells which lack C3 receptors respond to T-independent antigens. The precursors of PFC for the ABA epitope reside largely or exclusively in the CRL(+) compartment in A/J mice, whereas precursors for the DNP determinant are found in both compartments.

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PubMed1975

Augmentation of marrow growth by thymocytes separated by discontinuous albumin density-gradient centrifugation.

Mouse thymocytes were separated by discontinuous albumin density-gradient centrifugation. The ability of B6 thymocytes from the gradient fractions to increase the number of spleen nodules formed by B6 marrow cells in B6D2F1 recipients was compared with that of similar numbers of B6 thymocytes from an unfractionated cell suspension. Thymocytes from any of the gradient fractions were not more effective than thymocytes from an unfractionated suspension in augmenting marrow-cell growth, indicating that the presumptive 'effective cell type' in this system cannot be separated from the total thymocyte population by its buoyant density properties.

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PubMed1972

Antigen recognition and the immune response. "Self-help" with symmetrical bifunctional antigen molecules.

L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.

Animals↗
PubMed1972

Antigen recognition and the immune response. Structural requirements in the side chain of tyrosine for immuno-genicity of L-tyrosine-azobenzenearsonate.

The low molecular weight compound L-tyrosine-azobenzenearsonate (RAT) induces a cellular immune response in guinea pigs. The contribution of the side chain of tyrosine to the immunogenicity of RAT and the structural requirements at that position for immunogenicity were assessed by synthesizing a series of analogs of RAT containing modifications in the side chain of tyrosine and employing them as immunogens. Removal of either the carboxyl or amino group did not markedly affect immunogenicity, measured by the induction of delayed cutaneous sensitivity, whereas deletion of both completely abolished it. However, a charged group was not required since side chains containing a polar hydroxyl group could substitute for chains bearing an amino or carboxyl group. The size of the side chain exerted a pronounced influence; the charged or polar substituent had to be extended from the phenolic ring by at least two carbon atoms in order to confer immunogenicity.

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