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E S Vitetta

Publications and source records attributed to E S Vitetta.

At least 217 records · Page 12Linked to original sources
PubMed1983

T cell-derived B cell growth and differentiation factors. Dichotomy between the responsiveness of B cells from adult and neonatal mice.

In these studies we have determined the molecular weights of B cell growth factor (BCGF) (less than 20,000), and B cell differentiation factors (BCDF) that induce immunoglobulin M (IgM) secretion (BCDF mu) (30-60,000) and IgG secretion (BCDF gamma) (less than 20,000). Thus, the molecular weight of BCDF mu is distinct from that of BCGF and BCDF gamma; BCGF and BCDF gamma cannot be distinguished. In addition, BCGF, BCDF mu, and BCDF gamma are distinguishable by their presence or absence in different supernatants from a panel of mitogen-induced T cell clones. These results suggest that the three lymphokines are different. This conclusion is supported by their differential biological effect on B cells from adult and neonatal mice. Thus, treatment with anti-Ig induces B cells from adult mice to proliferate and this proliferation is sustained by BCGF. In contrast, even in the presence of BCGF, anti-Ig does not induce B cells from neonatal mice to proliferate. However, BCDF mu and BCDF gamma induce IgM and IgG secretion in B cells, respectively, from both adult and neonatal mice. Thus, mature B cells can both clonally expand and differentiate in response to anti-Ig, BCGF, and BCDF, whereas immature B cells can only differentiate. The poor response of neonatal B cells to anti-Ig and BCGF may partially explain the relative immunoincompetence of immature B cells.

Aging↗
PubMed1983

Structural studies of cell surface and secreted IgG in LPS-stimulated murine B cells.

We have characterized the cell surface IgG of LPS-stimulated B lymphocytes by surface iodination and specific immunoprecipitation. IgG3 was found to be the predominant IgG subclass expressed on the B cell surface after 5 days of stimulation with LPS. In contrast, IgG2b, IgG3, and IgG1 subclasses are all secreted. Cell surface IgG exhibits detergent binding characteristics not shown by secreted IgG and the gamma chains of the three subclasses of surface IgG examined have the apparent mol. wt of 64 Kd, some 9,000 larger than the H chains of secreted IgG.

Animals↗
PubMed1983

Synergy of ricin A chain-containing immunotoxins and ricin B chain-containing immunotoxins in in vitro killing of neoplastic human B cells.

A strategy is described for improving the efficacy of ricin A chain-containing immunotoxins. Highly purified preparations of ricin A chain or ricin B chain were separately coupled to anti-human immunoglobulin antibodies and the conjugates (immunotoxins) were affinity purified to eliminate free chains. Mixtures of anti-Ig-A and anti-Ig-B immunotoxins markedly synergized in vitro in their ability to kill the Ig-bearing human lymphoma cell line Daudi. In contrast, A-chain- or B-chain-containing immunotoxins of irrelevant specificity did not synergize with anti-Ig-A or anti-Ig-B immunotoxins. This finding indicates that free A or B chains do not play a major role in the synergy and that the synergy is specific. Thus, synergy depends on the specificity of the two antibodies; the lectin binding ability of a B-chain-containing immunotoxin of irrelevant specificity does not suffice. This approach of delivering ricin A chain and B chain separately to a target cell may have significant advantages in killing cells that are not effectively killed by A-chain-containing immunotoxins alone.

Burkitt Lymphoma↗
PubMed1983

Activation of antigen-specific B cells: role of T cells, cytokines, and antigen in induction of growth and differentiation.

T cells and cytokines were used to activate highly enriched populations of 2,4,6-trinitrophenyl (TNP)-binding B cells (TNP-ABC). TNP-ABC did not proliferate or differentiate when they were cultured with thymus-dependent (TD) antigen, even in the presence of supernatants known to contain B-cell growth and differentiation factors. However, purified TNP-ABC did proliferate and differentiate when they were cultured with TD antigen in the presence of carrier-primed T cells and antigen (TNP-keyhole limpet hemocyanin)--i.e., linked recognition. TNP-ABC blasts generated under conditions of linked recognition proliferated and differentiated in response to cytokines in the absence of T cells and antigen. In contrast, under conditions of nonlinked recognition (hapten and carrier on different molecules) TNP-ABC blasts also proliferated but did not differentiate in response to the same cytokines. These results indicate that antigen-specific "resting" B cells must be activated by T cells and antigen prior to becoming responsive to cytokines. Furthermore, activation under conditions of linked and nonlinked recognition generates two different types of blasts with regard to their subsequent response to cytokines.

Animals↗
PubMed1983

Induction of proliferation and differentiation of murine B cells bearing surface Ig lambda by rat monoclonal antibody to lambda chain.

Rats were immunized with the purified BCL1-IgM lambda 3(1) and their spleen cells were fused with Sp2/0 cells. Hybridomas secreting antibodies reactive with lambda 1-, lambda 2-, and lambda 3-containing myeloma proteins were subcloned and propagated in spinner culture. The antibodies were tested in a solid-phase radioimmunoassay and by indirect immunofluorescence using either BCL1 cells or normal mouse spleen cells. One of the monoclonal antibodies was purified to 95% homogeneity on DEAE-Sephadex. The purified anti-lambda anti-body, coupled to Sepharose, was mitogenic for lambda-bearing normal B cells and BCL1 cells, and in the presence of a supernatant from Concanavalin-A (Con A) stimulated these cells to secrete IgM lambda.

Animals↗
PubMed1983

A partial characterization of suppressor cells in the spleens of mice conditioned with fractionated total lymphoid irradiation (TLI).

Total lymphoid irradiation (TLI) is a highly effective modality for inducing immunosuppression and transplantation tolerance. The cellular basis for this immunosuppression is not clear, although T cells have been implicated. To study further the effect of TLI on the immune system, we have examined the B cells and suppressor cells in the spleens from TLI-conditioned mice. Our results indicate that after TLI, the spleen is rapidly repopulated with many large, immature cells. The probable source of these cells is the shielded bone marrow (BM). The B cells from TLI-conditioned mice are transiently immature and hyporesponsive in vitro to a T-independent antigen. Spleen cells from TLI-conditioned mice nonspecifically suppress the in vitro T-independent anti-TNP response of normal B cells. The suppressor cells lack both B and T cell markers and adhere to Sephadex G-10. The suppressor cells in spleens from TLI-treated mice bear a number of similarities to those present in normal BM. When normal BM cells were analyzed by indirect immunofluorescence for the presence of the Mac-1 antigen, two populations of suppressor cells could be identified: one was Mac-1+ and the other was Mac-1-. These data are consistent with the possibility that a subpopulation of the suppressor cells found in normal BM and in the spleens from TLI-conditioned mice are immature cells of the monocytic/granulocytic lineage.

Animals↗
PubMed1983

The use of haptenated immunoglobulins to induce B cell tolerance in vitro. The roles of hapten density and the Fc portion of the immunoglobulin carrier.

The relationship between the Fc region of trinitrophenylated (TNP)-immunoglobulins (Ig), and their ability to induce tolerance was examined. It was found that adult B cells responding to a T-independent (TI) antigen were tolerized by TNP11 human gamma globulin (HGG), but not by TNP10F(ab')2 fragments of HGG. Increasing the hapten density on the F(ab')2 fragments overcame their inability to induce tolerance. Thus, a TNP17-F(ab')2 was an effective tolerogen. Murine myeloma proteins of different IgG subclasses were similarly tested. A TNP12-IgG2a and a TNP11-IgG1 induced tolerance, whereas two TNP11-12-IgG3 did not. However, a more heavily haptenated TNP18-IgG3 was tolerogenic. These results suggest that lightly haptenated immunoglobulins depend upon Fc receptor binding to induce tolerance in adult B cells. Non-Fc receptor-binding carriers are not tolerogenic unless they are more heavily haptenated. Finally, T cell and macrophage depletion experiments suggest that the tolerogens act directly on the B cells.

Animals↗
PubMed1983

Suppression and elimination of BCL1 leukemia by allogeneic bone marrow transplantation.

Mice carrying the B cell leukemia (BCL1)+ were successfully treated by total lymphoid irradiation (TLI), cyclophosphamide, and allogeneic bone marrow (BM) transplantation. Long-term survivors were examined for residual BCL1 cells and for the ability to transfer adoptively graft vs. leukemia (GVL) activity. Residual BCL1 cells could not be detected in the allogeneic BM chimeras (greater than 14 to 16 months) with the use of indirect immunofluorescent staining with anti-idiotype antibody. However, residual tumor cells were present in 50% of the "cured" chimeric mice since adoptive transfer of 10(6) spleen cells from 50% of the treated chimeric mice caused leukemia in BALB/c recipients. In order to determine whether leukemia had been prevented in the "cured" chimeras by a persistent cell-mediated mechanism, BALB/c mice were injected with 10(6) spleen cells from the "cured" BM chimeras together with a dose of 10(2) or 5 x 10(5) BCL1 cells. Onset of leukemia was delayed or completely abolished in a significant proportion of recipients receiving the cell mixtures, suggesting the presence of anti-tumor immunity in the cured mice. The data suggest that a persistent active immune mechanism may be responsible, in part, for the significant antileukemic effects observed in mice tolerant to donor alloantigens.

Animals↗
PubMed1983

Quantitative monitoring of lymphoid malignancies. Application and findings in chronic lymphocytic leukemia.

The present study investigated the surface immunoglobulin (Ig) phenotypic pattern in 64 cases of chronic lymphocytic leukemia (CLL). The fluorescence activated cell sorter techniques were modified to provide sensitive and highly reproducible detection and quantification of the otherwise faint surface immunoglobulins on the cells in CLL. In over 98% of the cases of CLL, light chain of the surface Ig could be identified and measured. Serial measurements were shown to be highly reproducible. The phenotypic pattern and density identified on the surface of the circulating lymphocytes precisely reflected the findings in any given patient when other lymphoid tissue (bone marrow, lymph node or spleen) was sampled. Intraclonal heterogeneity detected by surface Ig was seen in some cases of CLL in spite of a relatively uniform morphology by other classical techniques. Three patterns of cell-to-cell variation were seen: 1) that of a non-Gaussian distribution of surface light Ig staining intensity 2) that of the presence of increased surface light Ig chain on a portion of the cells with a subpopulation of CLL cells showing an additional class of heavy chain, and 3) that of anisotropy where the surface Ig quantitatively did not correlate with cell size. Immunoglobulin phenotypic characterization of the cases of CLL was correlated with their clinical stage of disease activity. The distribution of surface light chain phenotype did not relate to any pattern of clinical stage of activity of the disease. By contrast, cases where the cells had a predominance of surface IgM were associated with a more advanced stage of CLL and a poorer clinical prognosis. When surface IgG was predominant, a lesser degree of clinical activity of disease was identified. The phenotypic pattern of the surface Ig on the lymphocytes in CLL mirrors the pattern of differentiation in the murine model of B-cell differentiation, and clinical aggressiveness appears to correlate with the character and degree of B-cell differentiation.

Animals↗
PubMed1983

Use of an antibody-ricin A-chain conjugate to delete neoplastic B cells from human bone marrow.

Affinity-purified rabbit antibody to human lambda and kappa chains (R alpha H lambda kappa) was conjugated to the A-chain of the plant toxin, ricin. The resulting immunotoxin (R alpha H lambda kappa-A) killed cells from the tumor cell line Daudi, which bears surface immunoglobulin, but was nontoxic to the CFU-E, BFU-E, and CFU-GM of human bone marrow. R alpha H lambda kappa-A eliminated 99% of clonogenic Daudi cells that had been mixed with marrow cells in vitro, without demonstrable toxicity to hematopoietic cells. Thus, in vitro treatment of marrow with R alpha H lambda kappa-A may increase the incidence of cure following autologous bone marrow transplantation for the treatment of human B-cell malignancies.

Antibodies, Anti-Idiotypic↗
PubMed1983

Activation of antigen-enriched b cells. I. Purification and response to thymus-independent antigens.

The development of a procedure for the selection of a large number of functional antigen-binding B cells is described. Forty to 70% of the cells in the enriched population bind antigen, and the antigen-binding can be inhibited by pretreatment with either the free hapten (TNP-Lys) or anti-immunoglobulin. The enriched cells express both slgM and slgD and respond to mitogenic stimuli by proliferating and developing into antibody-forming cells. In contrast to normal spleen cells, however, the enriched cells also proliferate in response to submitogenic levels of TNP-Brucella abortus and TNP-LPS.

Animals↗
PubMed1983

Activation of antigen-enriched B cells. II. Role of linked recognition in B cell proliferation to thymus-dependent antigens.

The responsiveness to T-dependent (TD) and T-independent (TI) TNP-antigens of murine splenic B cells previously enriched for antigen-binding cells (ABC) was examined. TNP-TI antigens induced B cell proliferation. TNP-TD antigens did not induce a proliferative response regardless of the physical form or nature of the TNP-TD antigen (e.g., soluble vs particulate, low or high haptenation of carrier, TNP on various insoluble matrices, etc.). TNP-TD antigens were effective in enhancing the response of the TNP-ABC to all concentrations of lipopolysaccharide (LPS) tested, indicating that binding of antigen to surface immunoglobulin alters the LPS responsiveness of the cell. Irradiated, keyhole limpet hemocyanin- (KLH) primed T cells induced a threefold to fourfold greater B cell proliferative response with TNP-KLH than with fluoresceinated KLH (FLU-KLH) or FLU-KLH together with TNP-human serum albumin (TNP-HSA). Therefore, linked recognition appears essential for optimal T cell-mediated B cell proliferation, whereas the induction of B cell proliferation via nonlinked, carrier-activated T cells is a minor component of the response.

Animals↗
PubMed1983

Effect of T cell-derived lymphokines containing B cell differentiation factor(s) for IgG (BCDF gamma) on gamma-specific mRNA in murine B cells.

Cytoplasmic RNA was isolated from cells cultured with LPS and LPS plus a T cell-derived supernatant (SN) (PK 7.1) containing B cell differentiation factors. The steady state levels of isotype-specific mRNA were assessed by Northern blot analysis with gamma-specific CH3 probes. It was demonstrated that the SN induces an increase in the level of mRNA for gamma 1 and a concomitant decrease in the levels of mRNA for gamma 2b and gamma 3.

Animals↗
PubMed1982

In vivo therapy of a murine B cell tumor (BCL1) using antibody-ricin A chain immunotoxins.

Prolonged remissions were induced in mice bearing advanced BCL1 tumors by the combined approach of nonspecific cytoreductive therapy and administration of a tumor-reactive immunotoxin. Thus, the vast majority of the tumor cells (approximately 95%) were first killed by nonspecific cytoreductive therapy using total lymphoid irradiation (TLI) and splenectomy. The residual tumor cells were then eliminated by intravenous administration of an anti-delta immunotoxin. In three of four experiments, all animals treated in the above fashion appeared tumor free 12-16 wk later. In one experiment, blood cells from the mice in remission were transferred to normal BALB/c recipients, and the latter animals have not developed detectable tumor for the 6 mo of observation. Because 1-10 adoptively transferred BCL1 cells will cause tumor in normal BALB/c mice by 12 wk, the inability to transfer tumor to recipients might indicate that the donor animals were tumor free. In the remainder of the animals treated with the tumor-reactive immunotoxin there was a substantial remission in all animals, but the disease eventually reappeared. In contrast, all mice treated with the control immunotoxin or antibody alone relapsed significantly earlier (3-4 wk after splenectomy).

Animals↗
PubMed1982

T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells.

Culturing BALB/c B cells for 6 d at low cell density in the presence of lipopolysaccharide (LPS) results in the appearance of a small number of IgG plaque-forming cells (PFC). The addition of supernatants from concanavalin A (Con A)-induced alloreactive (AKR anti-B6) long-term T cell lines (PK 7.1.1a and 7.1.2) or a T cell hybridoma (FS7-6.18) to LPS-treated B cells resulted in a marked increase in IgG PFC (3--10-fold higher than in cultures treated with LPS alone. The number of induced IgG PFC was not affected by removing IgG-bearing cells on the fluorescence-activated cell sorter, indicating that T cell-derived B cell differentiation factor enhances isotype switching of sIgG- cells, rather than selecting and expanding pre-existing subpopulations of sIgG+ cells. We also investigated the subclass of IgG produced in the absence or presence of T cell factors and found that PK 7.1.1a, PK 7.1.2, and FS7-6.18 supernatants selectively increased IgG1 production. Several other T cell supernatants containing a variety of lymphokines had no effect, suggesting that PK 7.1.1a, PK 7.1.2, and FS7-6.18 lines produce factor(s) that can specifically enhance the recovery of IgG secreting cells in culture in the presence of LPS. These factors, which we have termed B cell differentiation factors, are different from interleukin 1, interleukin 2, T cell-replacing factor, colony-stimulating factor, macrophage-activating factor, and immune interferon. Our results suggest that soluble factors produced by T cell lines and hybridomas can markedly influence both the class and subclass of Ig produced by B cells.

Animals↗