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Biomedical subjects

S Strober

Publications and source records attributed to S Strober.

216 records · Page 12Linked to original sources
PubMed1973

Maturation of B lymphocytes in the rat. I. Migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive antidinitrophenyl response.

The migration pattern, tissue distribution, and turnover rate of unprimed and primed B lymphocytes involved in the adoptive anti-DNP response was studied. The adoptive primary response restored by unprimed spleen or thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) was markedly diminished as compared with that restored by unpassaged cells. On the other hand, the adoptive response restored by passaged spleen or thoracic duct cells from DNP-primed donors was greater than or the same as that restored with unpassaged cells, respectively. This suggests that unprimed B cells change from nonrecirculating to recirculating lymphocytes after exposure to antigen. Studies of the adoptive anti-DNP response restored by unprimed or primed bone marrow cells showed little change in the time-course or amplitude of the response restored by either population of cells. The relative inability of marrow cells to carry immunological memory was related to the inability of recirculating memory cells to penetrate the marrow. The turnover rate of unprimed and primed B cells was investigated by treating the cell donors with [(3)H]thymidine for 48 h before removal of thoracic duct or spleen cells. The adoptive anti-DNP response restored by unprimed or primed cells was not affected by [(3)H]thymidine treatment. This indicates that both populations of cells turn over slowly. However, our previous studies show that unprimed B cells involved in the adoptive antibody response to ferritin turn over rapidly. The different findings are discussed in the context of antigen-dependent B-cell maturation.

Animals↗
PubMed1973

Biological characteristics of T and B memory lymphocytes in the rat.

The adoptive secondary antibody response of rats to the hapten-protein conjugate dinitrophenyl-diphtheria toxoid (DNP-DT) was used to investigate the migratory properties and rate of formation of T and B memory cells in the spleen. The experimental findings show that hapten (DNP-BSA)- and carrier (DT)-primed spleen cells act synergistically in the restoration of the adoptive anti-DNP response. Passage of both hapten- and carrier-primed spleen cells through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed that both cell types are able to recirculate from the blood to the lymph. In addition, memory to the hapten or carrier could be withdrawn from the spleen by prolonged thoracic duct drainage. The rate of formation of hapten- and carrier-primed spleen cells was studied by treating donors with [(3)H]thymidine for 48 h before cell transfer in an attempt to "suicide" rapidly dividing cells. Only a slight reduction in the adoptive response to the hapten or carrier was noted upon transfer of treated cells to irradiated hosts. In further experiments, the cell lineage of hapten- and carrier-primed cells was determined by treating each cell type in vitro with rabbit antirat B cell serum (RARBS) and complement. Although treatment with RARBS did not affect the adoptive response restored by carrier-primed cells, the same treatment abolished the response restored by hapten-primed cells. These findings indicate that T and B memory cells in the spleen of the rat are relatively long-lived, recirculating lymphocytes. The contribution of fixed or rapidly turning over cells to immunological memory is small or negligible as compared with the latter cells.

Animals↗
PubMed1972

Initiation of antibody responses by different classes of lymphocytes. V. Fundamental changes in the physiological characteristics of virgin thymus-independent ("B") lymphocytes and "B" memory cells.

The life-span and migratory characteristics of rat thoracic duct cells which initiate the adoptive primary and secondary antibody response to diphtheria toxoid (DT) and horse spleen ferritin (HSF) were investigated. The experimental results show that thoracic duct lymphocytes from normal (unimmunized) donors are able to restore the adoptive response of irradiated hosts to HSF. Thoracic duct cells passaged through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed a marked reduction in their restorative action as compared with unpassaged cells. In addition, the restorative action of cells from donors treated with thymidine-(3)H for 48 hr before cannulation of the thoracic duct was markedly decreased. This indicates that a population of lymphocytes involved in the adoptive primary response is unable to recirculate from the blood to the lymph and is turning over rapidly (short lived). The nonrecirculating, short-lived lymphocytes are proably "B" cells, since a combination of spleen cells from neonatally thymectomized rats and passaged or thymidine-(3)H-treated cells restores a vigorous response to HSF. On the other hand, passaged or thymidine-(3)H-treated thoracic duct cells from donors immunized to DT or HSF are able to restore a vigorous adoptive secondary antibody response. Experiments with the hapten-protein conjugate, DNP-DT, show that the majority of both helper ("T") and precursor ("B") cells are able to recirculate and are slowly turning over (long lived). The findings suggest that T lymphocytes involved in both the primary and secondary antibody response are recirculating, long-lived cells. However, B lymphocytes involved in the primary response are nonrecirculating, short-lived cells ("B(1)" cells) which undergo a fundamental physiological change to recirculating, long-lived cells ("B(2)" cells) involved in the secondary antibody response.

Aminocaproates↗
PubMed1972

Induction of immunological tolerance to soluble histocompatibility-2 antigens of mice.

Immunological tolerance to a soluble, partially purified fraction of histocompatibility (H)-2(a) antigen was induced in B10.D2 strain mice. The fraction used was obtained after chromatography on a Sephadex G-150 column. Tolerance of humoral-antibody formation (cytotoxins and hemagglutinins) was observed in mice injected with soluble antigen since birth, but cell-mediated immunity, as measured by skin graft survival, remained intact. Tolerance was shown to be specific for H-2(a) antigens, since treated mice produced a regular humoral-antibody response to H-2(b) antigens. These findings, along with previous observations of the immunogenic and enhancing properties of our partially purified fraction, suggest that the solubilized antigen contains all the major determinants of H-2(a) antigens expressed on lymphoid-cell surfaces.

Animals↗
PubMed1971

Immunologic enhancement of allogeneic tumor growth with soluble histocompatibility-2 antigens.

Soluble, partially purified, histocompatibility antigens that were obtained from the membranes of A/J spleen cells have been assayed for their capacity to elicit immunologic enhancement of two tumors of A-strain origin: YAA-C1 and Sarcoma I. Crude membrane material and a partially purified, soluble antigen that were contained in a specific fraction, obtained after chromatography on a Sephadex G-150 column, elicited enhancement; this fraction has been shown to contain immunogenic histocompatibility-2(a) antigens as well as alloantigenic specificities that were detected serologically. Another soluble fraction did not induce enhancement; this fraction has been shown to contain antigens other than H-2. Passive enhancement of both tumors was achieved with antisera produced in allogeneic mice that were inoculated with crude membrane material or with a fraction obtained by Sephadex G-150 chromatography. These antisera contained cytotoxic and/or hemagglutinating antibodies. Immunologic enhancement was specific. A readily enhanceable tumor, Py 89, of C57BL origin was not enhanced with anti-H-2(a) antisera. These results suggest strongly that all important H-2(a) transplantation antigenic determinants of spleen cells can be recovered by partial papain digestion and fractionation on a Sephadex G-150 column.

Animals↗
PubMed1970

Serological and immunogenic activity of soluble mouse transplantation antigens controlled by the H-2 locus.

The solubilization and partial purification of mouse transplantation antigens were monitored by (1) an in vitro assay for alloantigenic specificities and (2) an in vivo assay for transplantation antigens controlled by the H-2 histocompatibility locus. Antigens from A/J mice were solubilized by papain and fractionated on a Sephadex G-150 column. The eluate showed a 280 nm absorbance peak (F(1)) in the excluded volume and two peaks (F(2) and F(3)) in the included volume. H-2 specificities 1, 3, 4, 5, 11, 23, and 28 were confined to a single peak in the F(2) fraction. Fractions F(1), F(2), and F(3), were tested for their ability to accelerate skin graft rejection in noncoisogenic strains which differ at both H-2 and non-H-2 loci, and coisogenic strains which differ only at the H-2 locus. All fractions produced significant acceleration of graft rejection in the noncoisogenic strains, but only fraction F(2) produced significant acceleration in the coisogenic strains. These findings indicate that H-2 transplantation antigens detected by our in vivo assay, and H-2 alloantigenic specificities detected by our in vitro assay are solubilized by papain and are eluted in the same peak during Sephadex fractionation.

Alleles↗
PubMed1969

Initiation of antibody responses by different classes of lymphocytes. I. Types of thoracic duct lymphocytes involved in primary antibody responses of rats.

Thoracic duct cells and spleen cells were tested for their ability to restore the primary antibody response of X-irradiated rats to bovine serum albumin (BSA), sheep red blood cells (SRBC), horse spleen femtin (HSF), and Salmonella typhi flagella. Spleen cells were at least as efficient as thoracic duct cells in restoring the response to BSA, HSF, and Salmonella typhi flagella. In further experiments thoracic duct cells lacking large dividing lymphocytes were tested for their ability to restore the primary response. Large lymphocytes were eliminated by the in vitro incubation of thoracic duct cells for 24 hr at 37 degrees C or by treatment of thoracic duct cell donors with the mitotic inhibitor vinblastine sulfate 24 hr prior to cannulation of the thoracic duct. Experiments with SRBC show that incubated cells and cells from vinblastine-treated donors are as efficient as normal cells in restoring the primary antibody response. On the other hand, experiments with HSF and Salmonella typhi flagella show that incubated cells and cells from vinblastine-treated donors are about five times less efficient than normal cells in restoring the response. Normal thoracic duct cells were more efficient than incubated cells but less efficient than cells from vinblastine-treated donors in restoring the early response to BSA. The experimental findings indicate that the classes of thoracic duct lymphocytes which initiate the primary antibody response to SRBC differ from the classes which initiate the response to HSF and Salmonella typhi flagella, or BSA.

Agglutination↗
PubMed1969

Further studies on the role of circulating lymphocytes in the initiation of primary antibody responses to different antigens.

Thoracic duct cells obtained from normal (unimmunized) donors restored the primary hemolysin response of lethally irradiated or neonatally thymectomized rats to sheep red blood cells. Synergy between thoracic duct cells and bone-marrow cells was demonstrated in the irradiated hosts. However, thoracic duct cells did not restore the primary antibody response of irradiated rats challenged with diphtheria toxoid, but did restore the response of neonatally thymectomized rats. The addition of peritoneal exudate cells or bone-marrow cells to inocula of thoracic duct cells also failed to restore the response of irradiated hosts to diphtheria toxoid, although normal spleen cells restored the response. These findings indicate that the cellular events involved in the initiation of the primary antibody response to sheep red blood cells differ from those involved in the response to diphtheria toxoid.

Animals↗
PubMedDate not supplied

Total lymphoid irradiation for treatment of intractable cardiac allograft rejection.

The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for "salvage" therapy of cardiac allograft rejection unresponsive to conventional therapy.

Adult↗