Characterization of T and B antigen-binding cells for beta-galactosidase. II. T antigen-binding cells.

The results reported in this paper suggest that the specific Z-binding cells of the normal mouse include a large portion of T lymphocytes. Depletion of T cells with anti-theta serum and cortisone indicates that the majority of the ZBC of the thymus, which occur at frequencies of about 150/10(6), are indeed T cells. Similar treatment of spleen cells suggests that approximately half the binding cells in that organ are contributed by the T lymphocyte population. T-and B-enriched populations obtained from the spleen by using differential adherence to nylon wool contained equal numbers of ZBC and bound equivalent amounts of the antigen. Hence, there appears to be a high frequency of T lymphocytes that can be shown to bind beta-galactosidase specifically in both the thymus and spleen of normal mice.     

Avian antigen-binding cells. II. Enrichment of antigen-binding B and T cells.

Antigen-binding B and T cells from chicken spleens were selected on plates of antigen-derived gelatin. Hapten-specific B cells from DNP-immune normal chicken spleens were selected on DNP-gelatin. As much as 165-fold functional enrichment of precursors of anti-DNP antibody-producing cells, as measured in an adoptive transfer system, was achieved. However, the enrichment of DNP-binding cells assessed by rosette formation and autoradiography was no more than 25-fold. HGG-specific T cells from bursectomized agammaglobulinemic chickens immunized with deaggregated HGG were selected on HGG-gelatin. In the fraction adherent to HGG-gelatin, at least a 20-fold enrichment of suppressors of the antibody response to TNP-HGG, as measured by adoptive transfer, was accomplished. In contrast, no more than 6-fold enrichment of HGG-binding cells was detected by autoradiography. Antigen-specific depletion and enrichment of suppressor T cells and of HGG-binding cells occurred in parallel, suggesting that suppressor cells can bind soluble antigen and can be isolated on antigen coupled to a solid support.     

Circulating T and B lymphocytes of the mouse. I. Migratory properties

Studies on the identity of thoracic duct lymphocytes (TDL⁴) from normal and T cell-depleted mice indicated that as many circulating B lymphocytes were produced by healthy T cell-depleted mice as normal mice. Proportions of T and B cells from the thoracic duct of CBA mice changed markedly during the first 4 days of drainage from 82% T cells and 16% B cells at 12 hr to approximately equal proportions of both classes after 3 days. In absolute terms, T cells were mobilized rapidly by thoracic duct drainage and B cells very slowly. Histologically, this was reflected in a rapid depletion of the T cell-dependent areas of the lymphoid organs. The B cell-dependent areas, in contrast, became depleted of lymphocytes only after drainage for a week or more.The homing properties of circulating lymphocytes were investigated using TDL from normal and T cell-depleted mice as relatively pure sources of T and B cells, respectively. Four hours after injection of ⁵¹Cr-labeled T and B cells, a large proportion of both cell classes were found in the spleen. By 24 hr, many T cells had left the spleen and appeared in the lymph nodes. Such redistribution by B cells, however, was minimal.Intravenously injected T and B cells, labeled with tritiated uridine (³HU), localized specifically in the T and B cell-dependent areas, respectively, of the lymphoid tissues.³HU-labeled T cells were found to recirculate rapidly from blood to lymph. Labeled B cells, in contrast, recirculated only very slowly.     

Avian antigen-binding cells. I. Characterization of antigen-binding T cells from bursectiomized chickens by autoradiography.

Antigen-binding cells (ABC) from spleens of HGG-immunized, bursectomized agammaglobulinemic (Bx) chickens were detected by direct autoradiography with 125I-HGG and by sandwich autoradiography with HGG plus 125I-goat-anti-HGG. The specificity of antigen binding was demonstrated by 1) inhibition of binding of 125I-HGG by preincubation with unlabeled HGG and 2) a specific increase in ABC after immunization. The ABC from Bx chickens were not B cells, as shown by the virtual absence of immunoglobulin-bearing cells in this population and by the lack of inhibition of antigen binding by anti-immunoglobulin sera. The ABC were not macrophages and did not bind HGG via Fc receptors because their frequency was unchanged after passage over nylon wool or incubation with antigen-antibody complexes. The temperature dependence and azide stabilization of the ABC were characteristic of antigen-binding T cells. Therefore, T cells capable of binding soluble antigen were demonstrated in Bx chicken spleen, which is free of contamination by B cells and passively adsorbed antibody.     

Studies on the capacity of B cells as well as T cells to serve as accessory cells for the activation of herpes simplex virus-specific cytolytic T cells

Experiments were conducted in an effort to determine the ability of B and T lymphocytes to serve as APC for the activation of HSV-primed splenic T cells to become class I-restricted, HSV-specific CTL. The results showed that both freshly isolated splenic B cells as well as LPS and dextran sulfate (L/D)-activated B cells were effective at stimulating the generation of CTL during a 5-day in vitro culture. There was no requirement for the addition of exogenous IL-2 to the culture and, since murine B cells do not appear to express either membrane or secreted IL-1, this lymphokine appears to either not be required for the activation of virus-specific CTL or to be provided by the T cells themselves. When normal B cells were separated into fractions enriched for resting vs activated cells and then tested for their ability to stimulate the generation of HSV-specific CTL, it was found that while the activated B cells were quite effective at stimulating the generation of CTL, resting B cells were ineffective at carrying out this function. In contrast to normal B cells, normal T cells were unable to act as APC. However, Con A-activated T lymphoblasts were equivalent to L/D B cells in their ability to mediate the generation of CTL activity. L/D B cells that had been pulsed with HSV and then incubated at 37 degrees C for greater than 1 h could be fixed with paraformaldehyde and were still able to function as APC. The finding that L/D B cells, that had been fixed at 1 h or less after exposure to HSV, were unable to function as APC suggested that either active Ag "processing" steps may be required for the presentation of Ag in the context of class I molecules or that there is a requirement for the synthesis of viral protein Ag before presentation.     

Specific antigen-binding and antibody-secreting lymphocytes associated with the erythrocyte autoantibody responses of NZB and genetically unrelated mice.

The receptor characteristics as well as incidence of antigen-binding lymphocytes (ABL) or B and T cell classes with membrane receptors specific for the exposed (X) and cryptic (HB) murine erythrocyte autoantigens were examined in NZB and nine control strains of mice. Whereas only NZB and NZB hybrid mice synthesize anti-X autoantibody pathogenetically implicated in the genetically determined autoimmune hemolytic anemia, the NZB as well as control strains synthesize the ubiquitous anti-HB anti-erythrocyte autoantibody. By utilizing immunocytoadherence assays, maximum numbers of specific ABL of both B and T lymphocyte classes were optimally demonstrated at erythrocyte:lymphocyte ratios of 20:1 and after lymphocyte fixation at 56 degrees C for 20 min. Surface membrane receptor specificity was established by inhibition with semi-purified soluble X or HB autoantigen. Inhibition of immunocyto-adherence with class specific antisera to mouse immuno-globulins demonstrated that the receptors on both B and T cells were of IgM class. Specific receptors regenerated in vitro after trypsinization which excluded the role of cytophilic antibody in the immunocytoadherence reactions. B lymphocyte ABL reactive with the X autoantigen were demonstrable in NZB, NZB hybrid, and control mice. Only in NZB and NZB hybrid mice, strains that uniformly synthesize anti-X autoantibody, were X ABL of T lymphocyte class demonstrated. The presence and incidence of T lymphocyte X ABL is compatible with the expression of a single dominant gene carried by the NAB strain. The incidence of B lymphocyte X ABL increased with age, suggesting proliferation of this cell population. HB ABL of both B and T lymphocyte classes were observed in all strains, concordant with the ubiquitous presence of humoral anti-HB autoantibodies. Differentiation of precursor B cells are evaluated by PFC assay of cells secreting specific autoantibodies. Anti-X PFC were observed only in NZB and NZB hybrid mice; and the observed frequency suggested that less than 3.5% of the specific ABL were differentiated for the secretion of anti-X autoantibody. Anti-HB PFC were observed in all strains and represented as high as 11.8% of specific ABL. Genetic determination of the anti-X anti-erythrocyte autoantibody response does not prescribe the presence of precursors of the antibody-forming cell, but rather appears to influence regulation of the differentiation of these cells. These data suggest that circumvention of immunologic tolerance to this specific erythrocyte autoantigen may occur at the level of the T lymphocyte; or alternatively, that T lymphocytes as well as B lymphocytes, are induced to proliferate and differentiate in the NZB strain.     

Ontogeny of thymic B cells in normal mice.

Ontogeny of thymic B cells and their surface characteristics were analyzed using monoclonal antibodies (mAbs) against B220 molecules (CD45, CD45R). A small number of B cells were detected in fetal thymus on Gestation Day 14 (approximately 3.5% of the low-density fraction). Similarly, the percentage of B cells in the low-density fraction was 3.2% on Gestation Day 18, and 3.5% on Day 1 after birth. These were the same level as that of adult mice. CD5+ B cells, which form the major population of thymic B cells, were also found in the fetal life (0.5% on Day 14 and 2.2% on Day 16 in the low-density cells). The percentage of CD5+ B cells in B cell-enriched fraction was about 65% on Day 1 after birth, which is the same level as that in adult mice. These results indicate that a small number of B cells or cells in the B-cell lineage are present in the fetal thymus and also suggest the importance of these thymic B cells in the negative selection of T cells during early developmental stages.     

An immunofluorescence analysis of the ontogeny of myeloid, T, and B lineage cells in mouse hemopoietic tissues

The population dynamics of granulopoietic cells, B-lineage cells, and T lymphocytes were analyzed by immunofluorescence in mouse hemopoietic tissues as a function of age. Mac-1+ myeloid cells were present on day 11 of gestation in the liver, where they peaked shortly after birth and declined subsequently. Waves of myeloid population growth began in spleen and bone marrow by days 15 and 19, respectively. Mac-1+ cells increased in number to relatively low plateau levels in spleen by the 3rd wk after birth, whereas in the bone marrow higher plateau levels were reached around 3 mo of age. The 14.8 monoclonal antibody was utilized as one marker of B-lineage precursor cells. 14.8+ cells were detected in the liver on day 11 of gestation, reached peak numbers during the first week after birth and decreased thereafter. On day 15 and 19, 14.8+ cells were found in spleen and bone marrow, respectively, and progressively increased in numbers to reach plateau levels in both sites by 3 mo of age. Mu+ pre-B cells appeared in significant numbers in the 13-day fetal liver, reached a peak shortly after birth, and disappeared from the liver by the end of the second postnatal week. Pre-B cells were found in the spleen and bone marrow on days 15 and 19, respectively. In the spleen pre-B cells reached peak values at birth and disappeared 2 wk later. In spite of the sequential appearance of mu+ pre-B cells in fetal liver, spleen, and bone marrow, their sIgM+ B cell progeny appeared in all these hemopoietic tissues on day 17 of gestation. In the liver, sIgM+ B cells reached their peak at birth and declined thereafter. In the spleen and bone marrow, B cells increased to plateau levels between 1 and 4 mo of age. Thy-1.2+ T cells were relatively late acquisitions in all three hemopoietic tissues. Finally, the expression of the 14.8 antigen by mu+ cells was examined as a function of gestational age. While pre-B cells from day-13 fetuses had no detectable 14.8 antigen, the antigen was weakly expressed on the vast majority of the mu+ pre-B cells by day 17 of gestation. Newborn liver cells expressing 14.8 antigen were found to include a small proportion of cells with peroxidase+ granules. Thus, demonstration of rearrangement and expression of immunoglobulin genes may be required for precise identification of cells of B lineage early in ontogeny.     

Suppressor cells as an agent of immune facilitation. II. Adoptive transfer of passively induced enhancement of allografted tumors

CBA mice injected intravenously with CBA anti-A/J spleen cell antiserum, and challenged subcutaneously 24 hr later with A/J-derived sarcoma 1 (Sa 1) develop progressive tumors. “Normal” CBA mice (i.e., injected with normal CBA serum or noninjected) reject the allograft within 20 days. Spleen cells taken from mice 20–35 days after the injection of antiserum and Sa 1 challenge can specifically transfer the ability to enhance tumor growth when injected into 200 rad irradiated recipients. Spleen cells taken 8 days after antiserum and Sa 1 challenge cannot transfer suppression. The induction of suppressor cells requires both antiserum treatment and Sa 1 challenge. Serum from suppressed mice, and from control mice that are rejecting their tumors, can also transfer suppression but only when taken 20–35 days after treatment. The suppressor cells function most effectively when transferred at the time of tumor challenge, however, they also inhibit the rejection of Sa 1 when mixed with nylon-wool purified sensitized T cells. Suppressor cells are both nylon-wool nonadherent and adherent. Further purification of the column-enriched cells using antiimmunoglobulin or anti-Thy 1.2, plus complement, suggests that both T and B cells can suppress. The mixed lymphocyte response (MLR) of spleen cells from mice challenged only with Sa 1 is inhibited 8 days after challenge. A secondary response is obtained at 20–27 days. In contrast, the MLR from antiserum and Sa 1-treated mice 8 days after challenge resembles a secondary response. By 20–27 days mice with progressive tumors have only a primary-like response. In the present experimental situation, mitomycin-treated spleen cells from antiserum and Sa 1-treated mice cannot significantly inhibit the MLR of normal cells.     

Antigen and receptor-driven regulatory mechanisms. VI. Demonstration of cross-reactive idiotypic determinants on azobenzenearsonate-specific antigen-binding suppressor T cells producing soluble suppressor factor(s)

The first detectable suppressor T cell (Ts) arising after i.v. administration of azobenzenearsonate- (ABA) conjugated syngeneic spleen cells to A/J mice has been studied for its receptor specificity and ability to produce soluble suppressor factor(s). This cell, termed Ts1, has a specific receptor for the eliciting antigen ABA, as demonstrated by selective binding to ABA protein- but not TNP protein-coated plastic dishes. The activity of ABA-Ts1 can be abrogated by treatment with anti-idiotypic antibodies made against anti-ABA antibodies of A/J mice (anti-CRI), indicating that these ABA-binding cells possess a surface receptor structure sharing idiotypic determinants with antibodies of the same specificity. Finally, soluble extracts from, antigen-adherent ABA-Ts1, but not nonadherent cells from the same spleen cell population, possess suppressive activity when assayed directly for afferent suppression or tested for their ability to trigger a second population of Ts (Ts2) in naive recipients. These findings demonstrate a close concordance between a T cell surface receptor, soluble T suppressor factors, and B cell derived antibody, all capable of direct recognition of the eliciting ABA antigen.     

Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice

B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mice genetically deficient in B cells (NOD.Kmu(null)) or rendered B cell-deficient by treatment from birth with anti-IgM develop minimal SAT. B cells were required some time in the first 4-6 wk after birth, because NOD.Kmu(null) or NOD.H-2h4 mice did not develop SAT when they were reconstituted with B cells as adults. The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cells as adults produced autoantibodies but did not develop SAT. B cell-deficient mice developed SAT if their T cells developed from bone marrow precursors in the presence of B cells. Because B cells are required early in life and their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4-6 wk after birth.     

T cell development in B cell-deficient mice. IV. The role of B cells as antigen-presenting cells in vivo

B cell-deficient, rabbit anti-mouse IgM-treated mice were compared with normal or normal rabbit immunoglobulin-treated controls in their ability to develop proliferative T cell responses, delayed hypersensitivity, and primary or secondary cytotoxic T cell responses. Immunization with hapten-coupled autologous spleen cells resulted in anti-mu-treated mice generating only marginal T cell responses. This decreased responsiveness was shown to be attributable not to an intrinsic T cell defect or to changes in the ability of macrophages from anti-mu-treated mice to present soluble antigen, but rather to the greatly diminished capacity of B cell-deficient spleen cells to present antigen. The results support the concept that B cells play a significant role in antigen presentation required for T cell activation.     

Requirement for B cells for activation of contrasuppressor T cells by type III pneumococcal polysaccharide

Type III pneumococcal polysaccharide (S3) is unable to activate S3-specific contrasuppressor T cells (Tcs) in mice depleted of B cells by chronic anti-IgM treatment or in immune defective xid mice that lack the B cell subset required for anti-S3 antibody responses. The inability of S3 to activate Tcs in xid mice was shown to be due to a requirement of B cells for Tcs activation rather than to an absence of Tcs in xid mice. The B cells from normal mice that are required for Tcs activation apparently function to present the S3 Ag to Tcs. S3 physically coupled to spleen cells (S3-SC) prepared from normal BCF1 SC could activate Tcs in both xid and BCF1 mice whereas S3-SC prepared from xid SC or B cell-depleted BCF1 SC could not activate Tcs in either strain. B cell APC function was abrogated by 3000 R irradiation and by treatment of the B cells with either chloroquine or paraformaldehyde. Interestingly, B cells from mice previously immunized with S3 were unable to function in Tcs activation; preimmunization of B cell donors with an irrelevant Ag or with a T-dependent form of S3 had no effect on their ability to function as APC. These latter observations are discussed in terms of the in vivo persistence of polysaccharide Ag and their ability to induce B cell tolerance under the experimental conditions used for these experiments. The results of this study provide evidence that B cells play an important and apparently obligatory role in the activation of Tcs by S3; B cells apparently function to present Ag to Tcs, resulting in the activation of this regulatory T cell subset.     

The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice

Mice rendered B cell deficient by treatment with rabbit anti-mouse IgM (anti-mu) antibodies from birth fail to respond when primed with soluble protein antigens in CFA, as measured by T cell proliferation when challenged with antigen in vitro. The role of B cells in T cell priming in vivo was examined by adoptively transferring hapten-specific B cells into anti-mu mice, followed by immunization with haptenated Ag in CFA. The T cell proliferative response to OVA of anti-mu BALB/c mice was partially restored by the administration of TNP or FITC-specific B cells and immunization with TNP-OVA or FITC-OVA, respectively. This reconstitution was Ag-specific, inasmuch as hapten-binding B cells restored the T cell responses to OVA in mice immunized with the same hapten coupled to OVA. The mechanism of B cell reconstitution of T cell priming in anti-mu mice was addressed using parental to F1 B cell transfers. The Ia restriction pattern of the activated T cells from these mice indicated that both direct presentation of Ag by transferred B cells and antibody-mediated enhancement of Ag presentation by non-B, host Ag-presenting cells occurred. Thus, Ag-specific B lymphocytes play a critical role in priming of T cells in vivo.     

Effects of neonatal anti-delta antibody treatment on the murine immune system. I. Suppression of development of surface IgD+ B cells and expansion of a surface IgM+ IgD- B lymphocyte population

Lymphocytes that bear surface (s) IgD make up the majority of B cells in mature mice and are the precursors of most antibody secreting cells in primary immune responses made by these mice. In order to study the functional capabilities of the minority sIgD- B lymphocyte population and to gain insight into the possible roles of sIgD, we attempted to abort the development of sigD+ B cells and to expand the sigM+IgD- B cell population by treating mice from birth with affinity-purified rabbit antibodies specific for mouse IgD (RaM delta). RaM delta-suppressed mice had no detectable sIgD+ spleen, lymph node, or bone marrow cells and, on average, only 20% as many sIgM+Ia+ splenic B cells as control mice but had normal numbers of splenic T cells. Lymph nodes from anti-delta suppressed mice were even more depleted of B cells than were spleens from these mice, whereas the percentage of bone marrow B cells in these mice was relatively normal. Germinal centers of anti-delta suppressed mice were fairly normal in appearance, whereas follicular mantle layers, the locus of most sIgD+ B cells in normal mice, were greatly depleted. In addition to their lack of sIgD, splenic B cells of anti-delta suppressed mice differed from those found in control mice in that they bore, on average, twice as much sIgM as control cells, and in that they included an increased percentage of large, DNA synthesizing cells as compared with spleen cells from control mice. However, most sIgM+IgD- splenic B cells from anti-delta suppressed mice were small, nonproliferating cells. B cells from anti-delta suppressed mice insert little or no sIgD into their cell membranes since they continued to bear no detectable sIgD 2 days after in vivo neutralization of RaM delta and since, unlike B cells from control mice, they failed to be activated by a single in vitro injection of a goat anti-mouse delta antibody. Despite their lack of sIgD+ B cells, anti-delta suppressed mice had relatively normal levels of serum IgG as well as normal to increased levels of serum IgM. Thus, sIgM+IgD- B cells appear to have the potential of differentiating into Ig secreting cells in vivo without acquiring sIgD.     

Inhibition of specific immune responses by feeding protein antigens. V. Induction of the tolerant state in the absence of specific suppressor T cells

The effect of CY pretreatment on the ability of OVA feeding to induce both tolerance and active suppression was examined in mice. CY-pretreated, OVA fed mice were fully unresponsive in both OVA-specific DTH and antibody responses, but, in contrast to untreated OVA-fed mice, did not transfer suppression to normal recipients via splenic lymphocytes. Restoration of Ts activity in CY-pretreated mice was accomplished by reconstitution with normal T cells before antigen feeding, indicating that the CY effect was at the Ts precursor level. In addition, it was found that certain OVA-specific immune parameters (DTH and splenic PFC responses) in recipient mice were susceptible to suppression by transfer of spleen cells from OVA-fed donors, whereas other measures (antigen-induced T cell proliferation and serum antibody titers) were not. The data suggest that CY-sensitive Ts are not necessary for either induction or maintenance of specific tolerance after OVA feeding.     

Slowly cycling (label-retaining) epidermal cells behave like clonogenic stem cells in vitro

Abstract. Slowly cycling label-retaining epidermal cells were identified by light microscopic autoradiography in the dorsal epidermis and hair follicles of adult mice 8–10 weeks after twice daily injection of [³H]dT on days three through five after birth. Pulse-labelled epidermal cells were identified in the epidermis and hair follicles of 7–8 week old mice 1 h after a single injection of [³H]dT at 8.00 a.m. For mice of both groups, epidermal cells including those from the hair follicles were harvested by trypsinization and were cultured from low density on feeder layers of irradiated Swiss mouse 3T3. On days 2, 4, 5, 7, 10 and 12, the cultures were fixed and processed for light microscopic autoradiography, and the distribution of labelled nuclei was quantified. On day 2 of culture, both label-retaining cells (LRC) and pulse labelled cells (PLC) were found primarily as single cells. After five days, LRC were found as pairs and clusters having silver grain counts consistent with their division. In contrast, PLC remained primarily as single cells. These results suggest that LRC may divide to form colonies (are clonogenic) whereas PLC are rarely clonogenic. The significance of this experiment is that it suggests that the LRC may not only be persistent in the epidermis, but that they may also be cells with relatively greater proliferative potential than the PLC and are thus likely to be stem cells.     

Mlsa generated suppressor cells. I. Suppression is mediated by double-negative (CD3+CD5+CD4-CD8-) alpha/beta T cell receptor-bearing cells.

Grafting of cells from B10.D2 (H-2d) donors into H-2 compatible lethally irradiated (DBA/2 x B10.D2)F1 hosts results in a severe graft-vs-host reaction (GVHR), developed against DBA/2 non-H-2 Ag, with only 0 to 10% of animals surviving. This GVHR mortality rate is dramatically reduced (90 to 100% of animals survive) by donor preimmunization against Mlsa determinants. The protection against GVHR correlates with a decreased B10.D2 anti-DBA/2 proliferative response in vitro. Both in vivo and in vitro phenomena are associated with activation of CD5+ suppressor T cells in the spleens of immunized mice. The present work was designed to study the origin of these suppressor cells and to further characterize their phenotype. The results show that significant suppression is not inducible in "B" mice. In contrast, in mice that were only thymectomized or else pretreated in vivo with anti-CD4 or anti-CD8 mAb, the suppressor cells are activated as efficiently as in normal mice. The suppression of GVHR mortality and proliferative responses in vitro is lost after depletion from preimmunized splenocytes of CD5+ T cells and remains unaltered after depletion of CD4+ or CD8+ T cells or both. Depletion of asialo GM1+ cells removes all NK activity, whereas the suppression is decreased only slightly. FACS analysis showed that double-negative (DN) cells from normal and immunized mice contain both CD3+ and CD3- cells; the vast majority of the CD3+ DN T cells express the alpha/beta T cell receptor. Suppression of GVHR and of proliferative responses in vitro are abrogated after elimination of CD3+ cells. These results suggest that Mlsa generated suppressor cells: 1) are derived from post-thymic long-lived T cell precursors; 2) are low asialo GM-1+ but do not exhibit NK activity; 3) belong to a subset of peripheral CD5+ DN T cells bearing a CD3-associated alpha/beta-heterodimer.     

The differential ability of splenic adherent cells from B6.lpr mice to induce suppressor T cells

Hapten-coupled splenic adherent cells or resident peritoneal cells from autoimmune B6.lpr mice that are over 5 mo of age fail to induce first-order inducer suppressor T cells (Ts1). However, the same population of hapten-coupled cells can induce both delayed-type hypersensitivity responses and third-order effector suppressor T cells (Ts3). Thus, splenic and peritoneal antigen-presenting cells from B6.lpr mice display a defined defect in the ability to induce certain suppressor T cell responses. The cellular defect in Ts1 induction is controlled by the lpr gene, since age-matched congenic B6 mice do not display this defect. The splenic adherent cell defect is temporarily correlated with the autoimmunity that develops in B6.lpr animals. The antigen-presenting defect in the B6.lpr splenic adherent population for Ts1 induction is reversible by culturing the cells in interferon-gamma. The results are discussed as an illustration of the relationship between experimental models of autoimmunity and defects in a suppressor T cell cascade.     

Early B-cell precursors in scid mice: normal numbers of cells transformable with Abelson murine leukemia virus (A-MuLV)

scid mice lack detectable B and T lymphocytes; there are no typical pre-B cells as defined by c mu and surface markers in their bone marrow and their thymus contains only 1% of the normal number of cells. In these characters scid mice seem to lack lymphoid stem cells. However, some mice have detectable serum immunoglobulin and others develop thymomas; both observations indicate that the block in lymphoid development is not absolute. To determine whether scid mice have any B-cell precursors, we looked for pre-B cells by their ability to be transformed by Abelson murine leukemia virus (A-MuLV). Surprisingly, scid mice contain as many B-cell precursors transformable with A-MuLV as normal control mice. Cell-surface markers specific for pre-B and B cells were detected on the A-MuLV-transformed bone marrow cells of both scid and normal mice, indicating that the A-MuLV-transformed cells belong to the B lineage. Interestingly, the same surface markers were undetectable on nontransformed scid bone marrow cells. We conclude from these results that scid mice have normal numbers of early B-cell precursors but that their differentiation into functional B cells is severely impaired.