bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes.
Authors: Theofilopoulos A N , Eisenberg R A , Bourdon M , Crowell J S , Dixon F J
Published: June 2004

The frequencies and absolute numbers of B and T cells in the lymphoid organs of five murine strains (NZB, (NZB X NZW)F1, BXSB, MRL/l, and MRL/n) with SLE-like syndromes were examined. We assessed the frequencies of cells bearing surface Ig, C3d and IgG Fc receptors, and theta-antigen. The sequential expression of Ig isotopes on developing B cells and the Ig isotypes expressed on adult B cells were ascertained. In addition, the Ly subsets and the expression of Ia antigens coded for by the I-J subregion of the mouse H-2 complex were examined. Compared to normal, older mice, New Zealand mice had low frequencies and absolute numbers of B cells, BXSB mice had a moderate B-cell proliferation, and MRL/l mice had normal absolute numbers of B cells but a reduced frequency concomitant with a massive T-cell proliferation. Old New Zealand mice and BXSB mice had reduced frequencies and absolute numbers of T cells compared to old controls. The developmental Ig-isotype diversity during the 1st wk of age was similar in normal mice and those with autoimmune manifestations. Mature B cells were present in lymphoid organs of New Zealand mice and BXSB mice as evidenced by the high frequency of C3d receptor-bearing cells and Ig-isotype expression (high ratio of IgM- to IgD-bearing cells) in adult spleen cells. Numbers of IgG Fc receptor-bearing cells were reduced in autoimmune mice with advanced age and disease. The proliferating T cells in MRL/l mice were found to be theta-antigen positive but Ly null. These theta+-, Ly null cells may have arisen from Ly123+ T cells. MRL/l and BXSB mice seemed normal in their content of T cells bearing Ia antigens coded for by the I-J subregion of H-2. Overall, mice with autoimmune manifestations appear to express perturbations in T and B cells with development of disease, and their patterns of change vary from one strain to another.
Mitogen-activated B-cell blasts reactive to more than one mitogen.
Authors: Andersson J , Coutinho A , Melchers F
Published: June 2004

One of three splenic B cells of 2- to 3-mo-old C57BL/6J or C3H/Tif mice are activated either by lipopolysaccharide (LPS) or by lipoprotein (LP) to grow and to mature to IgM-secreting cells. When mitogen-activated blast cells, after a 2-d activation period, are separated from nonactivated, small cells by velocity sedimentation, and no mitogen is readded, the blasts do not continue to grow but do continue to secrete IgM for several days. When the homologous mitogen is added for restimulation, the blast cells continue for several days to divide every 18 h and to develop IgM-secreting, plaque-forming cells. Frequency analyses at limiting dilutions of reactive B-blasts show that one cell in approximately equal to 1.2--1.5 blasts continue to grow and mature in the presence of the homologous mitogen, either LPS or LP. When the B-cell blasts obtained in a first activation period with either LPS or LP are restimulated with a heterologous mitogen, LPS, LP, Nocardia mitogen or mitogens contained in fetal calf serum a high proportion of the blasts continue to grow and mature to IgM-secreting cells. Frequency analyses show for LPS- or LP-blasts, restimulated in a heterologous fashion with either LP or LPS, that one cell in 1.35--1.5 blasts continue to divide and to mature to IgM-secreting cells. C3H/HeJ-splenic B-cells, which are LPS nonresponders, can only be activated to blast cells by LP. These LP-activated blasts can be restimulated by the homologous LP and by Nocardia mitogen and mitogens of fetal calf serum, but not by LPS. The results indicate that the majority of splenic B cells of 2- to 3-mo-old C57BL/6J or C3H/Tif mice are reactive to more than one B-cell mitogen. B cells, therefore, can possess in their surface membrane multireactive mitogen-receptor complexes which regulate growth and maturation.
HLA-linked genetic control of the specicity of human cytotoxic T-cell responses to influenza virus.
Authors: Shaw S , Biddison W E
Published: June 2004

We have investigated elements of the genetic control of human in vitro cytotoxic T-cell responses to influenza virus-infected autologous cells by studies of a large family. The pattern of virus-immune cytotoxicity among siblings demonstrated T-cell recognition of influenza virus predominantly (greater than 90%) in association with determinants which are coded by genes linked to HLA (P less than 0.0002). Many family members consistently generated cytotoxic activity against influenza predominantly in association with antigens coded by genes of only one of their HLA haplotypes. Such haplotype preferences were consistent among HLA-identical siblings, indicating that the specificity of the T-cell response to influenza virus in association with HLA-A and -B antigens is controlled by genes linked to HLA.
Identification and unusual tissue distribution of the canine and human homologues of Thy-1 (theta).
Authors: Dalchau R , Fabre J W
Published: June 2004

The tissue distribution of the canine and human homologues of Thy-1 were studied using quantitative absorption analyses of liver absorbed anti-brain xenosera assayed on thymus cells. Cross-reactivity studies with pure rat Thy-1 established that the assays were detecting the homologues of rat Thy-1. The results showed that the tissue distribution of Thy-1 varies remarkably between species. Canine Thy-1 was found in large amounts only on adult brain. It was present in much smaller amounts on thymus (8% compared with brain), and was also found on lymph node, spleen and bone marrow (3, 1 and 0.5%, respectively, compared with brain). Surprisingly, it was found on kidney in amounts equal to that on thymus. Studies with the fluorescence-activated cell sorter established that canine Thy-1 was present on all thymocytes and peripheral T lymphocytes. Neonatal thymus and kidney had adult levels of Thy-1, but only small amounts of Thy-1 were present on neonatal brain. In man, brain was again the only tissue to contain large amounts of Thy-1. Surprisingly, it was absent from human thymus, and present on human kidney in amounts roughly equivalent to that seen in the dog. It was absent from spleen, lymph node, bone marrow, liver, heart, erythrocytes, platelets, and serum. Cross-reactivity studies showed that dog and human Thy-1 showed extensive serological cross-reaction, and that the dog-rat and human-rat cross-reactive components were identical.
Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10.
Authors: Germain R N , Ju S T , Kipps T J , Benacerraf B , Dorf M E
Published: June 2004

T-cell derived suppressor factors (TsF) specific for the random copolymers L-glutamic acid60-L-alanine30-Ltyrosine10 and L-glutamic acid60-L-alanine40, referred to as GAT and GA, respectively, were prepared and partially purified on the approprate antigen immunoadsorbents. GAT-TsF obtained from nonresponder DBA/1 (H-2q) and SJL (H-2s) mice were passed over immunoadsorbents prepared from normal guinea pig serum (NGPS) or guinea pig anti-idiotype antiserum (anti-CGAT) specific for a common cross-reactive idiotype found on most anti-GAT antibodies in all mouse strains tested. Both the directly suppressive activity of the GAT-TsF and the ability of GAT-TsF to induce new suppressor T cells (Ts2) in vitro were adsorbed to and fully recoverable from the guinea pig anti-CGAT-Sepharose immunoadsorbent, while the TsF passed through the control NGPS-Sepharose without appreciable binding. The SJL GAT-TsF specifically eluted from anti-CGAT-immunoadsrobents was shown to still posses I-J determinants. These data provide evidence suggesting a sharing of V region structures between B-cell antibody and T-cell suppressor factor specific for an antigen (GAT) under Ir gene control, in agreement with earlier studies on T and B-cell alloreceptors, T-cell helper factors, and T and B-cell receptors for conventional antigens.
Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice.
Authors: Glaser M
Published: June 2004

When cyclophosphamide was administered to mice before immunization with syngeneic SV40 transformed cells, the specific immune response elicited, as was measured by in vitro 51Cr release assay was stronger and lasted longer when compared to the response generated in noncyclophosphamide-treated mice. The augmentation effect of the drug was dependent on cyclophosphamide concentration being optimal at 100 mg/kg and on the time of drug administration in relation to antigen immunization being optimal at 2 d before antigen administration. Transfer of T cells from normal syngeneic mice to drug-treated animals abolished the cyclophosphamide-induced augmentation of immune response. These results implied that cyclophosphamide sensitive T cells suppressed the in vivo generation of specific effector T cells against SV40-induced tumor-associated antigens.
Continuously proliferating allospecific T cells. I. Specificity of cooperation with allogeneic B cells in the humoral antibody response to sheep erythrocytes.
Authors: Waterfield J D , Dennert G , Swain S L , Dutton R W
Published: June 2004

Allospecific mouse T cells, positively selected in one-way mixed lymphocyte culture were maintained for 3 yr in tissue culture by sequential restimulation. Such proliferating T cells were tested for their ability to induce a positive allogeneic effect: activating B cells in an in vitro primary humoral response to sheep erythrocytes. It was found that such T lymphocytes could function as helper cells. Helper activity was shown to be specific in that the B cells activated had to share major histocompatibility complex (H-2) antigens with the strain used for selection of the cell line. Intra H-2 mapping showed that antigens coded in the IAk subregion played an important role in the induction of the positive allogeneic effect. Supernatant factors could substitute for the allogeneic T cells in activation of the in vitro humoral response. However, such supernates exhibited no strain specificity. Therefore, the specificity seen in the positive allogeneic effect is presumably a consequence of the alloantigenic recognition receptors intrinsic to the T cells, and not to any biologically restricting properties of the allogeneic effect factor itself.
Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes.
Authors: Bona C , Hooghe R , Cazenave P A , Leguérn C , Paul W E
Published: June 2004

The antibody response of BALB/c mice to trinitrophenyl (TNP)-levan or TNP-Nocardia water-soluble mitogen (NWSM) includes a small but significant fraction of antibodies which share idiotypes (Id) with the dinitrophenyl (DNP)- and TNP-binding myeloma protein MOPC-460. Active immunization of BALB/c mice with MOPC-460 or passive administration of anti-460-Id antibodies suppresses the 460-Id+ component of the anti-TNP response. By contrast, active immunization of BALB/c with anti-460-Id antibodies or passive administration of BALB/c anti-[anti-460-Id] antibodies leads to an enhanced 460-Id+ component in the anti-TNP antibodies produced in response to TNP-levan or TNP-NWSM. This enhanced 460-Id+ response appears to be a result of the elimination of suppressor T lymphocytes specific for the 460-Id as T lymphocytes from such mice are unable to suppress the in vitro 460-Id+ response to TNP-NWSM whereas normal T cells are suppressive. These results indicate that suppressor cells specific for 460-Id normally regulate the activation of precursors of cells capable of secreting 460-Id+ anti-TNP antibodies.
Three types of blood group I specificity among monoclonal anti-I autoantibodies revealed by analogues of a branched erythrocyte glycolipid.
Authors: Feizi T , Childs R A , Watanabe K , Hakomori S I
Published: June 2004

Blood group I activities of the purified glycosphingolipid lacto-N-iso-octaosyl ceramide (Fromula: see text) and 8 of its analogues have been evaluated with 11 anti-I sera including 5 anti-I sera previously tested. All but one of the antisera were inhibited by the lacto-N-iso-octaosyl structure. Three types of I-specificity could be distinguished although none of the anti-I sera was identical in its inhibition patterns with the nine glycophingolipid analogues. The anti-I sera Ma and Woj represent the first type and require an intact Galbeta1 leads to 4GlcNAcbeta1 leads to 6 chain, the anti-I sera Step, Gra, Ver, and Ful represent the second type which requires Galbeta1 leads to 4GlcNAcbeta1 leads to 3 chain with branching, and the anti-I sera Phi, Da, Sch, and Low belong to the third type which requires both branches to be intact. Anti-I antibodies varry in their ability to react with their antigenic determinants in the presence of external substitutions with alpha-linked galactose or sialic acid.
A dichotomy between the expression of IgD on B cells and its requirement for triggering such cells with two T-independent antigens
Authors: Buck LB , Yuan D , Vitetta ES
Published: June 2004

The majority of adult B lymphocytes in the mouse bear two immunoglobulin isotypes, IgM and IgD (μ(+)δ(+) cells) (1). A small population of IgM-bearing cells lacks, or expresses very low levels of IgD (μ- predominant [μp] cells) (1). These cells are believed to constitute a less mature subset of B cells analogous to neonatal B cells (2). Based on the time during ontogeny when responses to T-independent (TI) and T-dependent (TD) antigens appear (3, 4) and the ability to block in vitro responses with anti- μ or anti-δ (5, 6, D. Mosier, personal communication), it has been suggested that the precursors of two TI-1 responses, trinitrophenyl (TNP)- Brucella (TNP-BA) and TNP-lipopolysaccharide (TNP-LPS) are μp cells (5, 6), whereas the precursor for a TD response, TNP-sheep erythrocytes (TNP-SRBC), bears both IgM and IgD (6). However, the possibility cannot be excluded that IgD is present on some or all of the TI precursors, but that it is not obligatory for triggering.

In the present experiments we have examined the phenotypes of TI and TD precursors by treating cells with C' and either anti-μ or anti-δ before stimulation with antigen. Our results suggest that the majority of B cells that respond to TNP-BA, TNP-LPS, and TNP-SRBC bear IgD, even though in the case of the two TI antigens, IgD is not required for triggering.
Friend erythroleukemia antigen. A viral antigen specified by spleen focus-forming virus and differentiation antigen controlled by the Fv-2 locus.
Authors: Risser R
Published: June 2004

Serum from C57BL/6 (B6) mice hyperimmunized with NB-tropic Friend virus complex (FV) was cytotoxic for FV-induced erythroleukemic spleen cells and B6 Friend-murine leukemia virus (F-MuLV) lymphoma cells. Cytotoxic activity for erythroleukemia cells remained after repeated absorption of B6 anti-FV antiserum with Friend-Moloney-Rauscher MuLV lymphoma cells but was removed by absorption with erythroleukemia cells induced by FV or Rauscher Vrus. This serologic test system identified a previously unrecognized cell-surface antigen of mouse leukemia, designated Friend Erythroleukemia (FE) antigen to signify its appearance as a determinant of virally induced erythroleukemic differentiation. FE antigen was not detected on 15 transplanted or primary hematopoietic neoplasms, nor was it detected on cells infected with ecotropic, xenotropic, or dualtropic MuLV isolates in tissue culture. Two spleen focus-forming virus (SFFV) nonproducer cells of rats and one of mice express FE antigen in amounts comparable to primary erythroleukemia cells. Absorption tests with FE typing serum indicated that FE antigen was expressed on bone marrow and spleen but not thymus, lymph node, or peripheral blood of uninfected AKR, BALB/c, DBA, and SWR mice; all five tissues from B6 and C57L were negative. Quantitiative absorption tests indicated that the expression of FE antigen, though much lower than on erythroleukemic cells, was greatest on fetal liver, less on bone marrow, and lowest on spleen from BALB and SWR mice. Treatment of BALB/c or SWR fetal liver, bone marrow, spleen, thymus, or lymph node cells with FE typing serum did not result in significant lysis. These observations are consistent with the interpretation that FE antigen is expressed by a minor cell population present in fetal liver, bone marrow, and spleen. Expression of FE antigen, determined by absorption with bone marrow cells, cosegregated with inheritance of the Fv-2s allele in the 17 inbred, 7 recombinant inbred, and 4 congenic mouse strains tested. In summary, the FE antigenic system identifies a cell-surface determinant that has the properties of a SFFV-specified antigen and hematopoietic differentiation alloantigen controlled by the Fv-2 locus. The similarity of FE antigen to Abelson antigen may provide insight into the pathogenic properties of defective transforming MuLV.
Expression of xenotropic murine leukemia viruses as cell-surface gp70 in genetic crosses between strains DBA/2 and C57BL/6.
Authors: Morse H C , Chused T M , Hartley J W , Mathieson B J , Sharrow S O , Taylor B A
Published: June 2004

Flow microfluorometry was used to assess levels of xenotropic murine leukemia virus envelope-related cell-surface antigens (XenCSA) expressed on lymphocytes of mice derived from crosses between C57BL/6 (B6) and DBA/2 (D2); 24 recombinant inbred strains (BXD RIs) and 62 backcross mice were studied. The results suggest that XenCSA expression is affected by more than one gene but that the predominant influence is exerted by a single semidominant gene apparently located on chromosome 4 at or in close proximity to the Fv-1 locus. Studies of spontaneous virus production in B6D2F1 X D2 mice suggest that this locus may also affect production by spleen cells of xenotropic MuLV registering in a fluorescent antibody assay of mink lung cells.
Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo
Authors: Kasai M , Leclerc JC , McVay-Boudreau L , Shen FW , Cantor H
Published: June 2004

Relatively large numbers of nonimmune spleen cells do not protect against the local growth of two lymphomas. However, this heterogeneous population of splenic lymphocytes contains a subset of cells that efficiently protects against in vivo tumor growth. This cell population (cell-surface phenotype Thyl.2(-)Ig(-)Ly5.1(+)) represents less than 5 percent of the spleen cell population and is responsible for in vitro NK-mediated lysis.

Although these studies clearly and directly demonstrate that Ly5(+) NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of two different types of tumor cells (in contrast to other lymphocyte sets within the spleen), they do not directly bear upon the role of NK cells in immunosurveillance. They do indicate that highly enriched Ig(-)Thyl(-)Ly5(+) cells, which account for virtually all in vitro NK activity, can retard tumor growth in vivo.

It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. Perhaps NK ceils may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen, and portions of the gastrointestinal tract)and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may help to answer these questions.
Immune phagocytosis in murine malaria.
Authors: Shear H L , Nussenzweig R S , Bianco C
Published: June 2004

Spleen macrophages from Plasmodium berghei-infected mice are more efficient in the ingestion of parasitized reticulocytes than spleen macrophages obtained from normal animals. Other indications of spleen macrophage activation detected during malarial infection are enhanced macrophage spreading and increased phagocytosis of opsonized and nonopsonized sheep erythrocytes (E). Peritoneal macrophages are not activated to a significant degree. The appearance of antibodies directed against Forssman antigen, but not to other erythrocyte antigens, is also a feature of this infection and explains the ingestion of unsensitized E by spleen macrophages of the diseased animals. The recognition and ingestion of parasitized reticulocytes by infected mice in mediated by cold-agglutinin type immunoglobulins that appear during P. berghei infection and can be blocked by the Fc-binding protein A from Staphylococcus aureus. In advanced stages of the disease, the serum of infected animals inhibits phagocytosis, probably because of the high level of circulating immune complexes. Thus, the clearance of malaria parasites is regulated by several elements of the immune system, in addition to levels of specific antimerozoite antibodies, including the amount of antibodies bound to reticulocytes, the presence of circulating immune complexes, and the degree of macrophage stimulation.
The influence of steroid hormone metabolites on the in vitro development of erythroid colonies derived from human bone marrow.
Authors: Urabe A , Sassa S , Kappas A
Published: June 2004

Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin. Among a number of pairs of C5 epimeric steroids tested, most 5beta (A:B cis) steroids stimulated the growth of both early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E), whereas only a few 5alpha-(A:B trans) steroids stimulated the growth of CFU-E. No 5alpha-compounds of six pairs of steroids studied were found to stimulate BFU-E formation. This structure-activity relationship conforms with that previously observed in studies of steroid induction of ALA-synthase in avian embryo liver cells and hemoglobin synthesis in the cultured avian blastoderm. When human bone marrow cells were preincubated with the steroids for 2 d, followed by incubation with erythropoietin, only the 5 beta-compounds stimulated the growth of BFU-E. Similarly, when addition of steroids was delayed in relation to erythropoietin in the culture, only the 5 beta-derivative of a pair of C5 epimeric compounds displayed an enhancing effect on the growth of BFU-E. This effect required that the steroid addition be made no later than 48 h after initiation of the culture. These data demonstrate that certain natural steroid metabolites significantly stimulate erythropoiesis in normal human bone marrow cells in culture. They also indicate that 5 beta-compounds are more stimulatory than their 5 alpha-epimers, and they suggest that these 5 beta-steroids act preferentially on very primitive erythroid progenitor cells, probably on BFU-E.
Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. I. Genetic control of delayed-type hypersensitivity by VH and I-A-region genes.
Authors: Weinberger J Z , Greene M I , Benacerraf B , Dorf M E
Published: June 2004

Hapten-specific delayed-type hypersensitivity (DTH) was induced in several strains of mice. (4-hydroxy-3-nitrophenyl)acetyl-bovine gamma globulin (NP-BGG)-primed mice which did not bear the Ig1b heavy-chain linkage group made a NP-specific DTH response when challenged with NP bovine serum albumin (BSA) and failed to respond to challenge with (4-hydroxy-5-iodo-3-nitrophenyl)acetyl-bovine serum albumin (NIP-BSA). Strains of NP-BGG-primed mice bearing the Ig1b allotype, including SJL, responded to challenges of either NP-BSA or NIP-BSA. F1 hybrids between a cross-reactive strain, C57BL/6, and two other noncross-reactive strains were cross-reactive. Genetic mapping of the NIP-cross-reactive DTH response localized the trait to the VH-region of the Ig1b heavy-chain linkage group. The fine-specificity pattern of the T-cell anti-NP response, and the genetic mapping of this trait, were analogous to the reported fine specificity and mapping data of the humoral heteroclitic anti-NP response. Adoptive transfer studies on the ability to transfer NP-specific DTH between various strain combinations showed that the T-cell donors and the recipient must have homology for at least the I-A subregion. Whenever NP-specific reactivity was transferred from a strain which cross-reactively responded to NIP, the recipient also responded to both NP and NIP. The implications of the control of NP-primed DTH-reactive populations of T cells by two distinct genetic regions, VH and H-2, were discussed.
Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes.
Authors: Haller O , Arnheiter H , Lindenmann J
Published: June 2004

Radiation chimeras produced by crosswise transfers of bone-marrow cell among histocompatible mice susceptible, or genetically resistant, to lethal challenge by a number of myxoviruses were used to test whether macrophage resistance (as assessed in vitro) and resistance of the animal (as measured in vivo), both previously shown to be brought about by the gene Mx, were causally related. 49 chimeras were tested individually, both of resistance of their macrophages to in vitro challenge with M-TUR (a strain of avian influenza virus A/Turkey/England/63 adapted to grow in cultured mouse peritoneal macrophages), and for resistance of the animal in vivo upon challenge with pneumotropic, neurotropic, or hepatotropic influenza viruses. Cultivated Kupffer cells and peritoneal macrophages harvested from chimeric mice expressed the resistance phenotype of the bone-marrow donor irrespective of the host environment in which they had differentiated. However, susceptibility or resistance in vivo was according to the genotype of the host. Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system.
B-cell influences on the induction of allotype suppressor T cells
Authors: Black SJ , Herzenberg LA
Published: June 2004

Allotype suppressor T-cell (Ts) populations that persist for the life of the animal arise in (BALB/c × SJL)F(1) hybrids exposed perinatally to antibody to the paternal (Ig-1b) allotype on IgG(2a)-isotype immunoglobulin H chains. These Ts suppress Ig-lb production by depleting the supply of allotype- specific helper T cells (Th) required, in addition to carrier-specific Th, for the latter stages of Ig-1b memory B-cell differentiation.

In this publication, we show that specific Ig-1 allotype Ts are induced by perinatal exposure to antisera which interfere with normal B-cell maturation, i.e., by antibodies reactive with surface IgM on immature precursors of IgG(2a), memory cells. Antibodies to IgM (Ig-6) allotypes carried on precursors induce specific suppression for the IgG2, allotype produced by progeny of the target precursor. Anti-Ig-6a and anti-Ig-6b induce Ts that specifically suppress Ig-1a and Ig-1b, respectively. Heterologous (goat) anti-IgM induces suppression for both IgG(2a) immunoglobulins (Ig-1a and Ig-1b). Ts activity in these antiprecursor-Ig-suppressed mice is expressed in adoptive transfer assays and, as with anti-Ig-1b-induced Ts, is rendered ineffective by cotransfer of adequate numbers of T cells but not B cells from nonsuppressed mice. The Ts induction, in contrast with Ts expression, is reversed by the introduction of appropriate adult B-cell populations from nonsuppressed donors.

Taken together, these data suggest that the development of mature B cells plays a central role in the early establishment of the balance between helper cells and suppressor cells that determines whether Ts or Th will dominate in regulating Ig-1b production in adult animals.
Primary generation of cytolytic T lymphocytes in the absence of DNA synthesis.
Authors: MacDonald H R , Less R K
Published: June 2004

The requirement for DNA synthesis during the primary differentiation of cytolytic T lymphocytes (CTL) had been investigated. CTL were induced polyclonally in vitro by stimulation of normal C57BL/6 spleen cells with concanavalin A (Con A)and their cytolytic activity was tested against 51Cr-labeled target cells in the presence of Bacto Phytohemagglutinin M. With this system, CTL activity could first be detected 48 h after exposure of spleen cells to Con A. Addition of cytosine arabinoside at concentrations sufficient to reduce DNA synthesis by 95-98% in Con A-stimulated cultures did not significantly inhibit the generation of cytolytic activity on a cell-to-cell basis. These results demonstrate that derepression of the genetic information required for the expression of CTL function can occur in the absence of detectable DNA synthesis.
Two Plasmodium knowlesi-specific antigens on the surface of schizont-infected Rhesus monkey erythrocytes induce antibody production in immune hosts.
Authors: Schmidt-Ullrich R , Wallach D F , Lightholder J
Published: June 2004

Purified schizonts (6--10 nuclei) and membranes of schizont-infected erythrocytes from the Malaysian and Philippine strain of Plasmodium knowlesi are analyzed immunochemically using immunoglobulin of rhesus monkey hyperimmune sera against schizonts and of sera from naturally immune monkeys. The anti-schizont Ig identifies less than 20 immune components in Triton X-100-solubilized schizonts and membranes of infected cells. Of these antigens, 9 (component 1, 3, 4, 5, 6, 10, 11, 18, and 20) are common to parasites and membranes of infected erythrocytes, and 12 (2A,B, 6, 8, 9, 12, 13p, 14, 16A,B, 19 A,Bp, 21, 22p, and 23) are predominantly found in the parasite; 4 components (13i, 19A,Bi, 22A, B, and 24) are unique to the membrane of infected erythrocytes. Only three parasite-specific components (1, 13, and 19) are exposed on the surface of parasitized erythrocytes as revealed by both lactoperoxidase-catalyzed radioiodination and extensive absorption of anti-schizont Ig using intact infected erythrocytes. Two plasmodium-specific antigens (1 and 13) on the surface of infected erythrocytes are recognized by sera of rhesus monkeys rendered naturally immune against P. knowlesi infections and, therefore, represent antigens in vivo. Analyses of schizonts and membranes of parasitized erythrocytes of the two different strains of P. knowlesi yields only some minor quantitative, but no qualitative differences when analyzed with both types of antisera. Importantly, components 1 and 13 appear identical in both strains.
Regional blood flow and its relationship to lymphocyte and lymphoblast traffic during a primary immune reaction.
Authors: Ottaway C A , Parrott D M
Published: June 2004

The relationship of alterations in blood flow with changes in cell distribution has been studied in an inflammatory site and its draining lymph node during the induction of an immune reaction with oxazolone in mice. The cells which move to the site of inflammation are predominantly lymphoblasts and their increased localization in the inflamed ear is significantly correlated with increased regional blood flow to the inflamed tissue. The existence of this correlation is not antigen dependent although there is a relative increment of lymphoblasts which are specifically primed to the inflammatory agent. The localization of nonblastic (small) 51Cr-labeled lymphocytes on the other hand is substantial only in lymphoid tissue and during the induction of an immune reaction after oxazolone application, the increase in localization of these cells in the draining lymph node is positively correlated with increased blood flow to the node. Furthermore, the probability of finding 51Cr labeled lymphocytes in a particular lymph node is related to the regional blood flow which that node receives.
Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain.
Authors: Adorini L , Harvey M A , Miller A , Sercarz E E
Published: June 2004

We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.
Studies on the mechanisms of macrophage activation. II. Parasite destruction in macrophages activated by supernates from concanavalin A-stimulated lymphocytes.
Authors: Buchmüller Y , Mauel J
Published: June 2004

Activation of mouse peritoneal exudate macrophages, as evidenced by destruction of the intracellular protozoan parasite Leishmania enriettii, was obtained by incubation with supernates from concanavalin A (Con A)-stimulated syngeneic spleen cells. Parasites were not destroyed in macrophages exposed to control media. Supernate-induced activation was independent of the presence of Con A. The activating principle (macrophage activating factor, or MAF) was produced by Con A-stimulated lymphocytes in presence or absence of serum. In absence of serum, MAF synthesis was highest at Con A concentrations far below those required in serum-containing media. MAF production was reduced at Con A concentrations of 10 microgram/ml or above, probably a result of toxicity of the lectin for lymphocytes. MAF was detectable after 24 h of lymphocyte stimulation and increased up to 72 h; production appeared to be independent of DNA synthesis. Serum-free MAF was inactive when tested as such on macrophages. Full activity could be restored by addition of nanogram amounts of endotoxin or of FCS before assay. Endotoxin also considerably potentiated MAF activity in serum-containing supernates. Full intracellular parasite destruction was observed after contact of macrophages with MAF for 20 h. The continuous presence of MAF was not necessary for activation; a 10-h pulse was sufficient to induce macrophages to destroy all intracellular microorganisms within the next 38 h.
Failure of long surviving, passively enhanced kidney allografts to provoke T-dependent alloimmunity. I. Retransplantation of (AS X AUG)F1 kidneys into secondary AS recipients.
Authors: Batchelor J R , Welsh K I , Maynard A , Burgos H
Published: June 2004

Long survival of (AS X AUG)F1 rat kidney allografts in AS recipients was induced by passive enhancement with AS anti-AUG antiserum at the time of grafting. After 1-3 mo, the kidney allografts were transferred to second AS recipients, either naive or sensitized against AUG tissue. Naive second recipients did not reject the grafts acutely and failed to mount T-dependent immunity against AUG targets. When later challenged with spleen cells carrying the AUG haplotype, the naive second AS recipients showed strong IgM, IgG, and cytotoxic T-cell responses after grafting, and the kidneys were rapidly destroyed by immune rejection in all but one rat. It is concluded that long-surviving kidney allografts fail to activate helper T cells and induce in naive second recipients the same state of unresponsiveness observed in the first recipient.
Target-effector interaction in the human and murine natural killer system: specificity and xenogeneic reactivity of the solubilized natural killer-target structure complex and its loss in a somatic cell hybrid.
Authors: Roder J C , Ahrlund-Richter L , Jondal M
Published: June 2004

Preincubation of natural killer (NK) cells with electrophoresis purified proteins from a variety of NK-sensitive murine and human tumor cells specifically prevented subsequent binding to the intact, homologous target cell. The NK-target structures (NK-TS) consisted of some or all of four characteristic molecular species, tentatively assigned molecular weights of 140K, 160K, 190K, and 240K (+/-10K) based on electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels. When these NK-TS molecules were compared in cross-inhibition assays, the large 240K molecule most often carried the unique NK specificity, whereas the smaller 140K molecules cross-reacted between YAC, 136-6 and X-63 in the mouse and between Molt-4 and K562 in the human. Mouse NK cells recognised a different spectrum of NK-TS molecules than human NK cells. The control of NK-TS expression was partially revealed in a cloned, somatic cell hybrid bwtween an NK sensitive (YAC-IR) and insensitive (A9HT) cell line. The hybrid did not express NK-TS and did not bind to NK cells which is in accordance with negative NK cytolytic results previously reported. Although unique specificities are carried by some of the multiple NK-TS protein molecules, cross-reactions were widespread. These observations taken together suggest that the NK cell is polyspecific and has some heterogeneity in the recognition structure although much less than would be expected of an antibody-combining site.
Distribution of mast-cell precursors in hematopoeitic and lymphopoietic tissues of mice.
Authors: Kitamura Y , Shimada M , Go S , Matsuda H , Hatanaka K , Seki M
Published: June 2004

Two experimental systems were used to investigate the origin of precursor cells which differentiate into tissue mast cells in vivo. (a) Increase of mast cell number was examined in the skin, stomach, cecum, and mesentery of genetically mast cell-depleted WBB6F1 (WB X C57BL/6)-W/WV mice after the injection of various hematolymphoid cells of congenic +/+ mice. (b) Appearance of mast cells with giant granules was studied in irradiated C57BL/6-+/+ mice after the injection of lymphoid cells of C57BL/6-bgJ/bgJ (beige, Chediak-Higashi syndrome) mice. Concentrations of mast cell precursors in the thymus, lymph node and Peyer's patch were less than 0.1% of the concentration in the bone marrow. Neither treatment of donor bone marrow cells with anti-Thy-1.2 serum and complement nor thymectomy of the recipient mice affects the development of mast cells in the skin, stomach, cecum, and mesentery. Moreover, the number of mast cells increased to normal level when the skin of WBB6F1-W/WV mice was grafted on the back of nude athymic (BALB/c-nu/nu) mice. These results indicate that mast cell precursors are derived from hematopoietic tissues rather than lymphopoetic ones and that the differentiation of the precursor cells does not depend on T lymphocytes or the thymus.
Ability of antigen-specific helper cells to effect a class-restricted increase in total Ig-secreting cells in spleens after immunization with the antigen.
Authors: Rosenberg Y J , Chiller J M
Published: June 2004

Immunization with antigens stimulates not only B lymphocytes secreting specific antibody but, in addition, results in the generation of very large numbers of splenic Ig-secreting cells which lack specificity for that antigen. The present report examined the nature of the antigens capable of eliciting this effect and the mechanisms whereby B cells could be nonspecifically activated. It is shown that the ability of T-dependent, but not T-independent antigens, to induce such increases requires the participation of T helper cells specific for the antigen so that any one antigen results in the activation of only a proportion of total B cells. Analysis of this nonspecific plaque-forming-cell response reveals that B cell activation is not random but occurs in a class-restricted manner. The magnitude of the increase and the isotype produced are shown to be characteristic of the immunizing antigen. Based on the data presented, the apparent nonspecific T-B collaboration can best be explained by invoking a second Ig-specific helper mechanism in which helper cells capable of recognizing determinants on Ig molecules, e.g. isotype or idiotype, cause the stimulation of B cells of any specificity providing they express that determinant.
Effects of immobilized immune complexes on Fc- and complement-receptor function in resident and thioglycollate-elicited mouse peritoneal macrophages.
Authors: Michl J , Pieczonka M M , Unkeless J C , Silverstein S C
Published: June 2004

We have examined the Fc- and complement-receptor function of resident and thioglycollate-elicited mouse peritoneal macrophages plated on surfaces coated with rabbit antibody-antigen complexes and with complement. We derive four major conclusions from these studies. (a) The trypsin-resistant Fc receptors of resident and thioglycollate-elicited macrophages are completely modulated when these cells are plated on rabbit antibody-antigen complexes. Residual Fc receptor activity is a result of the incomplete modulation of trypsin-sensitive IgG2a receptors. (b) The complement receptors of thioglycollate-elicited macrophages, but not of resident macrophages, are modulated when these cells are plated on complement-coated surfaces. The capacity of the two cell types to modulate their complement receptors is correlated with their ability to ingest complement-coated erythrocytes. (c) The complement and Fc receptors of both types of macrophages move independently of one another. (d) Complement masks the Fc segments of IgG in immune complexes thereby rendering them ineffective as ligands for macrophage Fc receptors.
Genetic control of the immune response to collagen. II. Antibody responses produced in fetal liver restored radiation chimeras and thymus reconstituted F1 hybrid nude mice.
Authors: Hedrick S M , Watson J
Published: June 2004

The level of antibody produced in response to calf skin collagen in mice is influenced by genes which are closely linked to the I region of the H-2 major histocompatibility complex. This influence is shown to be expressed during lymphoid maturation by testing the antibody responsiveness to collagen in two types of chimeric mice. First, high responder and low responder parental strain mice were lethally irradiated and restored with fetal liver cells from (high X low responder) F1 mice. These F1 leads to parent chimeras exhibited an immune response phenotype characteristic of the irradiated parental strain animals, establishing that H-2 determinants of the host affect antigen responsiveness. Second, (high X low responder) F1 congenitally athymic (nude) mice were restored with fetal thymus transplants from either high or low responder parental strain mice. After a period of maturation these mice were shown to be competent for a T-dependent IgG response to SRBC. The responsiveness to collagen in these mice was characteristic of the parental strain thymus donors, indicating that the expression of H-2 determinants in thymic tissue during lymphoid maturation influences the antibody response phenotype expressed by mice.
H-Y antigen. Cell surface mapping and testosterone-induced supramolecular repatterning.
Authors: Flaherty L , Zimmerman D , Wachtel S S
Published: June 2004

Previous work with the antibody-blocking technique showed that the map of surface components for thymocytes prefixed with paraformaldehyde is the same as the map for unfixed thymocytes, with the following exception: after exposure to anti-TL or anti-Db, TL and H-2Db occupy adjacent positions on unfixed cells but not on fixed cells. This was interpreted as an indication that activation of particular components of the surface phenotype initiates ordered changes in the display of cell-surface molecules, approximation of TL and Db in this instance. These studies have now been extended to the H-Y component on the surface of male cells. On fixed male mouse thymocytes, H-Y lies adjacent to TL and relatively distant from H-2Db, H-2Kb, H-2Lb, Lyt-1.2, and Lyt-2.2. However, on unfixed male mouse thymocytes, similarly exposed to H-Y antibody, H-Y and H-2Db are adjacent. Presumably, this engagement of H-Y sites by H-Y antibody brings H-Y and H-2Db together. Evidence that this change in pattern may be physiologically relevant comes from the finding that testosterone, but not estradiol, caused the same selective approximation of H-Y and H-2Db.
Recognition among mice. Evidence from the use of a Y-maze differentially scented by congenic mice of different major histocompatibility types.
Authors: Yamazaki K , Yamaguchi M , Baranoski L , Bard J , Boyse E A , Thomas L
Published: June 2004

Previous studies of mating preference signified that mice can sense one another's major histocompatibility complex (MHC) types, probably by olfaction. This conclusion has now been substantiated by the use of a Y-maze whose two arms were differentially scented with currents of air conducted through boxes occupied by B6 (H-2b) males and by B6-H-2k congenic males. Four B6 mice, two males and two females, were successfully trained, by water deprivation and reward, to enter the arm scented by B6 or B6-H-2k males. One of the males and one of the females were trained to select the B6-scented arm; the other male and female were trained to select the B6-H-2k-scented arm. Untrained mice showed no MHC discrimination in the maze. The performance of the trained mice in distinguishing between MHC congenic homozygous F2 segregants derived from a cross of B6-H-2k with B6 was as good as their performance in distinguishing the respective inbred strains, thus essentially eliminating alternative and significant additional explanations of MHC-associated sensory discrimination. The data further indicate that chemosensory discrimination of MHC types can be entirely dissociated from sex differences and from the circumstances of mating.
Hapten-specific T-cell responses to 4-hydroxy-3-nitrophenyl acetyl. II. Demonstration of idiotypic determinants on suppressor T cells.
Authors: Weinberger J Z , Germain R N , Ju S T , Greene M I , Benacerraf B , Dorf M E
Published: June 2004

The ability of NP-coupled syngeneic spleen cells to induce antigen-specific T-suppressor cells capable of binding to NP-BSA-coated Petri dishes and mediating transfer of specific suppressive activity to NP was demonstrated. Furthermore, in strains of mice bearing the Ig-1b allotype, including SJL, and in (non-Ig-1b x Ig-1b)F1 hybrids, the NP-specific suppressor cells also interferes with expression of immunity after priming with NIP-BGG. Anti-NPb anti-idiotype antiserum plus complement treatment effectively abrogated the ability to transfer suppression. Formal genetic mapping of the fine specificity of cross-reactivity with Ig-1 allotypic congenic mice implies that expression of this trait is linked to the Ig-1b heavy chain linkage group. The sensitivity of NP-suppressor cells of appropriate strains to anti-idiotype treatment was also consistent with the formal mapping data. These experiments suggest that there are shared V-region structures on antibody and T cells that are crucial in the suppression pathway for the same antigen.