bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous regression of Friend virus-induced erythroleukemia. I. The role of the helper murine leukemia virus component.
Authors: Dietz M , Fouchey S P , Longley C , Rich M A , Furmanski P
Published: June 2004

The RFV strain of the Friend virus complex induces an erythroleukemia that spontaneously regresses. The tropism of regressing Friend virus complex (RFV), which is conferred by its helper MuLV component, MuLV-RF, is different from that of the conventional virus strain, CFV. RFV is NB-tropic and CFV is N-tropic. Passage of nonregressing CFV through Fv-1 incompatible Swiss/ICR mice changed the tropism of CFV from N to NB and resulted in a virus strain which induced erythroleukemia that regressed. Passage of NB-tropic CFV back through Fv-1 compatible mice maintained NB-tropism and regression. Altering the quantity or type of helper MuLV in RFV complex by addition of Ri-MuLV inhibited regression in proportion to the amount of added Ri-MuLV. These studies indicate a relationship between a change in virus tropism to NB by passage in certain hosts (e.g., Swiss/ICR mice) and the ability of Friend virus to induce erythroleukemia that spontaneously regresses. MuLV-RF isolated from the RFV complex induced lymphocytic leukemia in newborn mice which regressed and caused the regression of CFV-induced erythroleukemia. MuLV-RF is NB-tropic, contains no spleen focus-forming virus (SFFV) activity and helps SFFV form spleen foci in genetically restrictive mice. Pseudotype viruses were prepared, consisting of MuLV-RF, or other MuLV's, and SFFV derived from FV-B. The pseudotype viruses each acquired the tropism of the MuLV used in rescue. The pseudotype prepared with MuLV-RF or another NB-tropic MuLV-F, but not the virus obtained by rescue with N-tropic MuLV-F, induced erythroleukemia that spontaneously regressed. These studies demonstrate that the ability of RFV to induce erythroleukemia that spontaneously regresses is due to its helper MuLV component.
Experimental conditions for obtaining suppressor and helper effects on the primary in vitro immune response by lymphocytes activated by polyclonal T-cell activators.
Authors: Nespoli L , Möller G , Waterfield D , Ekstedt R
Published: June 2004

The effect of the polyclonal T-cell activators (PTA) Con A and PHA on the specific immune response to sheep red blood cells (SRC) was studied. Addition of PTA either enhanced or suppressed the anti-SRC response, and two variables were found to affect the results: time of addition of the PTA and the strength of the response in control cultures not given PTA. If the response was high, even suboptimal PTA concentrations induced suppressive effects, but if the control response was low, due to deficient batches of sera or because of the absence of serum, the addition of PTA increased the response or restored it to normal levels. Suppression could be obtained if the PTA were added before or at the same time as the antigen and required high (optimal) PTA concentrations. If addition was delayed for 12-24 h the suppressive effects disappeared and previously suppressive concentrations of the PTA now caused an enhanced response. Analogous results were obtained if preactivated lymphocytes were added to the cultures instead of soluble PTA. Neither Con A, PHA, or lymphocytes preactivated by these PTA suppressed the polyclonal response induced by LPS or PPD. Irrespective of the time of addition and the culture conditions, enhancement of the anti-SRC response occurred at lower PTA concentrations than suppression. It was concluded that suppressor T cells, if they exist, do not act on B cells, but rather on helper cells needed for induction of thymus-dependent responses. The findings in this system are not compatible with the existence of a specific subset of suppressor T cells, but rather with the notion that suppression is caused by too much help.
Antiviral protection by virus-immune cytotoxic T cells: infected target cells are lysed before infectious virus progeny is assembled.
Authors: Zinkernagel R M , Althage A
Published: June 2004

Virus-immune cytotoxic T cells can inhibit effectively growth of vaccinia virus in acutely infected target cells in vitro by destroying infected target cells before infectious virus progeny is assembled. Together with the fact that virus-specific T cells are demonstrable after 3 days, very early during infection, and with strong circumstantial evidence from adoptive transfer models in vivo, these data suggest that in some virus infections T cells may in fact act cytolytically in vivo to prevent virus growth and spread and be an important early antiviral effector mechanism.
Generation of T-helper cells in vitro. II. Analysis of supernates derived from T-helper cell cultures.
Authors: McDougal J S , Gordon D S
Published: June 2004

Supernates derived from in vitro generated T-helper cells have been analyzed for their capacity to substitute for T-cell carrier reactivity. T-helper cell supernates stimulate both a carrier-specific and nonspecific anti-DNP-PFC response to DNP-carrier conjugates in cultures of hapten-primed spleen cells. The carrier-specific and nonspecific activity can be distinguished by dosage optimum, antigen requirements, binding specificity for carrier, and in the requirement for additional splenic adherent accessory cell involvement. The active factors produced in this system are heat labile and sensitive to trypsin and periodate. They are removed by absorption with alloantisera directed toward the strain from which the supernate was derived but not by a variety of anti-immunoglobulin sera.
B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus- dependent and independent forms of the same hapten
Authors: Cambier JC , Vitetta ES , Uhr JW , JR Kettman
Published: June 2004

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those required to produce the same degree of unresponsiveness in neonates.

In contrast to these results, studies with T-independent (TI) antigens indicate that neonatal and adult splenic B cells are equally susceptible to tolerance induction (3,4). However, such studies have not ascertained whether the neonate is more resistant to tolerance induction or the adult is hypersusceptible, i.e., does the induction of tolerance in cells responsive to TI antigens resemble that of adult or neonatal cells responsive to TD antigens? The answer is pertinent to determining the relative maturity of the B cells which can be tolerized or respond to TI or TD antigens.

We report here the direct comparison of tolerogen sensitivity of adult and neonatal TD and TI responses by inducing tolerance in vitro with trinitophenyl human gamma globulin (TNP(17)HgG) and assaying unresponsiveness with TD and TI forms of the TNP determinant.
The monoclonality of human B-cell lymphomas.
Authors: Levy R , Warnke R , Dorfman R F , Haimovich J
Published: June 2004

Human tissues involved with lymphoma have been examined in frozen sections for immunoglobulin-bearing cells by a technique involving double-label immunofluorescence with mixed anti-kappa and anti-lambda antibodies. F (ab')2 fragments of purified antibodies were employed to avoid any binding via Fc receptors. B cell lymphomas were shown to be composed of monoclonal populations of Ig bearing cells, whereas normal or reactive lymphoid follicles contained a mosaic of Ig-bearing cells derived from multiple clones. Nodules of lymphoma were often surrounded by normal polyclonal B cell populations. We anticipates that the approach described here will be useful in the diagnosis of lymphoma, differentiating it from reactive lymphoid hyperplasia by the demostration of monoclonality. In addition, it should provide a sensitive and reliable tool for investigating the immunobiology of human lymphoma.
H-2 restriction of suppressor T-cell induction by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitization.
Authors: Miller S D , Sy M S , Claman H N
Published: June 2004

Studies using hapten-modified lymphoid cells as tolerogens for 1-fluoro-2,4-dinitrobenzene contact sensitization have shown that BALB/c(H-2d) mice can be made phenotypically tolerant by dinitrophenyl (DNP) on either syngeneic or allogeneic mouse lymphoid cells (DNP-LC). However, suppressor T-cell induction (Ts) in these mice (as demonstrated by adoptive transfer to syngeneic recipients) was restricted to H-2 identity between the DNP-LC and the donor mouse. It was also shown that identity at the right end of the H-2 complex was sufficient for Ts induction. In addition, this restriction was also demostrated in CBA (H-2 K) mice and for tolerance in the 1-chloro-2,4,6-trinitrobenzene contact sensitivity system using trinitrophenyl-modified lymphoid cells.
Immune mechanisms in leukemia role of the Ia antigens.
Authors: Lukasewycz O A , Frelinger J A
Published: June 2004

We have shown that the selective removal of cells possessing Ia determinants coded by the I-A, I-B, and I-J regions of the H-2 gene complex completely abrogates the protective capacity of nylon-wool-purified T lymphocytes against leukemic challenge. This suggests that the Ia antigen bearing T cells play an important role in tumor immunity.
Lymphocyte surface modulation and cyclic nucleotides I. Topographic correlation of cyclic adenosine 3':5'-monophosphate and immunoglobulin immunofluorescence during lymphocyte capping.
Authors: Earp H S , Utsinger P D , Yount W J , Logue M , Steiner A L
Published: June 2004

The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements.
Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice.
Authors: Kapp J A , Pierce C W , Benacerraf B
Published: June 2004

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.
The monoclonal anti-phosphorylcholine antibody response in several murine strains: genetic implications of a diverse repertoire.
Authors: Gearhart P J , Sigal N H , Klinman N R
Published: June 2004

The idiotypic identification of monoclonal antibodies has been used to define and enumerate clonotypes within the murine repertoire of B cells specific for phosphorylcholine (PC). The response in the BALB/c strain is dominated by a single antibody specificity which is identical to TEPC 15 protein; however, antibody without the TEPC 15 idiotype appears heterogeneous by idiotypic cross-reactivity and hapten inhibition of binding to antigen. Dissection of the PC-specific repertoire in the AKR, A/He, and C3H strains has indicated that some monoclonal antibodies share binding-site idiotypic determinants with TEPC 15, although these clones represent a minority of the precursor cells. In addition to providing insights into the heterogeneity and expression of the murine B-cell repertoire, these studies emphasize structural relationships between PC-specific clonotypes. Within the BALB/c strain, some antibodies share combining-site-related idiotypic specificities with TEPC 15, but differ in other variable region determinants. Among allotypically distinct strains, there exists a remarkable similarity of variable region determinants in at least a minority of antibodies.
The inheritance of antibody V regions in the rabbit: linkage of an H-chain-specific idiotype to immunoglobulin allotypes.
Authors: Yarmush M L , Sogn J A , Mudgett M , Kindt T J
Published: June 2004

Anti-idiotype antibodies specific for the H chain of an homogeneous antistreptococcal antibody (4135 Ab) were prepared by injection of recombinant molecules consisting of the H chains from 4135 Ab and L chains isolated from the injected rabbit. The antibodies prepared in this fashion (anti-HId) were specific for the VH region of 4135 Ab. Using this preparation in an inhibition of binding assay, sera from rabbits related and unrelated to 4135 were screened for the presence of the 4135 HId. It was found that about 45% of the related rabbits, when immunized with streptococcal Group C vaccine, produced antibodies with a cross-reactive idiotype, while less than 10% of similarly immunized unrelated rabbits produced molecules bearing HId. The expression of HId was linked to the a3 allotype present in the H chain allogroup J. Antibody molecules bearing the HId determinant were isolated from heterozygous (a1a3 and a2a3) rabbits and shown to express the a3 allotype. One rabbit lacking the a3 allotype produced significant amounts of antibodies expressing HId. These antibodies were found to express both VH and CH allo-types characteristic of the J allogroup, although neither allotype was found in a preimmune IgG sample from this rabbit.
Plasma levels of a viral protein as a diagnostic signal for the presence of mammary tumor: the effect of tumor removal.
Authors: Ritzi E , Martin D S , Stolfi R L , Spiegelman S
Published: June 2004

We have previously shown (1, 2) that mice with mammary tumors can always be identified by their very high plasma levels of gp52, a 52,000 mol wt glycoprotein of the mouse mammary tumor virus (MMTV). The present investigation demostrates that the tumor is the principal source of the plasma gp52 since surgical excision is invariably followed in the first 9 days by a sharp decreasing (10-100-fold) of the gp52 levels. Control animals in which the tumors were left in place by a "sham" surgical procedure maintained their high level of gp52, which continued to increase as the disease progressed. The behavior of the gp52 after surgical removal suggests that gp52 plasma concentrations are diagnostically and prognostically informative, as indicated by the following finding: (a) All tumor recurrences were correctly diagnosed by increases in gp52 levels, and some were detected 4-7 days before they were found by palpation. (b) Tumor regrowths were accompanied by continued increases in plasma gp52 concentrations at rates that usually matched the speed of tumor development. (c) The only animals that remained tumor free at the termination of the experiment were those that maintained their gp52 levels at or below 15 ng/ml. (d) The probability of a tumor-free animal relapsing within 2 wk is much higher if its gp52 level is above the mean. (e) More remarkably, the plasma levels of gp52 at the time of surgery are superior to the size of the tumors removed as prognostic indicators of eventual surgical "cures". The availability of a specific and sensitive systemic measure of disease status should augment the usefulness of the murine mammary tumor model by catalyzing a more rapid acquisition of information on the therapeutic effectiveness of the new and varied drug combinations being tested for adjuvant chemotherapy.
Hapten-specific delayed hypersensitivity to epsilon-2,4-dinitrophenyl-L-lysine-Ficoll in guinea pigs immunized with 2,4-dinitrophenyl-keyhole limpet hemocyanin.
Authors: McMaster P R , Owens J D , Dvorak H F , Weichbrod R , Asofsky R
Published: June 2004

After active immunization with 2,4-dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), 2,4-dinitropheynl-L-lysine (DNPL)-Ficoll may elicit indurated, erythematous skin reactions lasting 24-72 h. Histological sections of these reactions, examined by microscope techniques, showed they contained polymorphonuclear leukocytes and perivascularly situated lymphocytes and macrophages, but had very few basophils. Consequently, the reaction was interpreted as having an immediate component and a component typical of delayed hypersensitivity; this indicated that the delayed reaction could be specific for the DNP hapten. Although this delayed type of skin reaction was not transferred to recipients with anti-DNP-KLH serum, one pool of that serum did sensitize guinea pigs so that they could respond with a different skin reaction after challenge with DNPL-Ficoll. This reaction was soft, pale pink, and lasted for 24 h. Histologically, it contained only a few polymorphonuclear leukocytes. It differed from the delayed reaction in actively immunized animals in that it lacked induration, and was devoid of lymphocytes and macrophages.
Mechanisms of suppression of cytotoxic T-cell responses in murine lymphocytic choriomeningitis virus infection.
Authors: Dunlop M B , Blanden R V
Published: June 2004

The cytotoxic T-cell response to lymphocytic choriomeningitis (LCM) virus infection was suppressed either in vitro or in vivo by addition of a high level of syngeneic virus-infected cells or syngeneic cells from congenital LCM virus carriers to the environment of the responding cells. This effect was not duplicated by formaldehyde-fixed carrier cells, nor could it be accounted for by 'cold' target competition by carrier cells at the level of the cytotoxicity assay. Conversely, suppression was produced in vivo by water-lysed, ultrasonically treated carrier cell suspensions, or by a large dose of LCM virus equivalent to that contained in the carrier cells. Thus a high level of infectious virus was a common factor in all observed examples of suppression. Based upon this, the following hypothesis, a form of 'forbidden clone deletion,' was proposed to account for virus-specific cytotoxic T-cell tolerance in LCM virus congenital carriers, or in high dose suppression. A high level of virus in lymphoid tissues, while not cytopathic per se, may result in infection of all or most T cells; this then may lead to deletion either via 'suicide' of individual, infected, cytotoxic T cells with receptors specific for virus-induced antigenic patterns on their own surface membranes, or by mutual lysis of two adjacent T cells.
The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes II. Surface immunoglobulin isotopes on unprimed B cells in the spleen.
Authors: Zan-Bar I , Vitetta E S , Strober S
Published: June 2004

We investigated the ability of IgM-, IgD-, and IgG-bearing cells from the spleens of unprimed (BALB/c x C57BL/Ka)F1 mice to restore the adoptive primary anti-BSA and anti-DNP antibody responses. Purified populations of isotype-specific cells were prepared by immunofluorescent staining and sorting on the fluorescence activated cell sorter. Bright or dull cells were transferred to irradiated syngeneic recipients which were challenged with DNP-BSA in complete Freund's adjuvant. Unfractionated spleen cells as well as IgM- and IgD-bearing cells restored the adoptive primary IgM and IgG antibody response. IgG-bearing cells restored a vigorous adoptive response which was all IgG (2-mercaptoethanol resistant). Depletion of IgG-bearing cells markedly increased the adoptive IgM response, and depletion of IgM-bearing cells markedly increased the IgG response. However, depletion of IgD-bearing cells resulted in a considerable reduction in the IgG response. The latter finding indicates that there is a subpopulation of IgD-bearing cells which express little or no surface IgM and which make a considerable contribution to the adoptive primary IgG response.
Restriction of primary responses to the IgG class and dependency of IgM responses on secondary immunization for the copolymers of L-glutamic acid, L-tyrosine, and L-alanine.
Authors: Waltenbaugh C , Thèze J , Benacerraf B
Published: June 2004

Primary responses to the linear polymers of L-glutamic acid, L-tyrosine, and L-alanine are restricted to the IgG class of antibodies. The appearance of specific IgM antibodies against these antigens is dependent upon secondary immunization, in contrast to many classical antigenic systems. The presence of an IgM response was verified by a direct plaque-forming cell assay, the inhibition of direct plaques by an antiserum specific for mouse micron-chain, and the physical separation of IgM and IgG GAT-specific antibodies by gel filtration. Preimmunization of the appropriate nonresponder strain with GAT or GT inhibits both the secondary IgM and IgG responses to GAT-MBSA and GT-MBSA, respectively. The tolerance observed is due to the induction of suppressor cells as demonstrated by cell transfer experiments.
Regulation of B-cell proliferative responses to lipopolysaccharide by a subclass of thymus T cells.
Authors: Norcross M A , Smith R T
Published: June 2004

When thymus cells which are unresponsive to LPS are combined with numbers of peripheral lymphoid cells giving minimal responses to LPS, synergistic incorporation of [3H]thymidine occurs. Synergy requires that both components proliferate, but most of the augmented response is the result of peripheral cell proliferation. The thymus cell is a T cell of variable density, low in thy-1.2 antigen, not concanavalin A responsive, present in the major thymus subpopulation, and may be from lipopolysaccharide (LPS)-unresponsive strains. The peripheral cell is sensitive to anti-IgG or IgM plus complement (C'), resistant to anti-Thy-1.2 and C', exhibits adherence properties of B lymphocytes, and must be from LPS-responsive strains. Synergistic responses depend on critical thymus/peripheral cell ratios, inhibition occurring at high peripheral cell numbers. The data provide evidence that B-cell proliferative responses to LPS may be regulated by a subclass of thymus T cells.
Surface parasitism by Mycoplasma pneumoniae of respiratory epithelium.
Authors: Hu P C , Collier A M , Baseman J B
Published: June 2004

Identification of the attachment factor on virulent Mycoplasma pneumoniae organisms which permits surface parasitism of respiratory epithelium was attempted. Brief pretreatment of M. pneumoniae monolayers with protease prevented mycoplasma attachment ot sensitive host cells without reducing viability of the microorganisms. Gel electrophoretic analysis of mycoplasma proteins before and after exposure of intact mycoplasmas to protease revealed the absence of a major protein species (P1) in enzyme-treated preparations while other protein bands with the exception of P2 were virtually unaffected. The absence of P1 correlated with the failure of enzyme-treated mycoplasmas to attach to tracheal explants. P1 regeneration after protease treatment of mycoplasma monolayers was directly associated with reattachment capabilities in M. pneumoniae. Erythromycin inhibited P1 resynthesis, thus preventing resumed attachment activity by mycoplasmas. Lactoperoxidase-catalyzed iodination of intact M. pneumoniae organisms further confirmed that P1 was an external membrane protein and suggested that his surface component was required for the successful membrane-membrane interaction between host and parasite.
H-2 restriction of cell-mediated immunity to an intracellular bacterium: effector T cells are specific for Listeria antigen in association with H-21 region-coded self-markers.
Authors: Zinkernagel R M , Althage A , Adler B , Blanden R V , Davidson W F , Kees U , Dunlop M B , Shreffler D C
Published: June 2004

The protective activity of anti-Listeria-immune T cells assayed in an adoptive transfer system in H-2 restricted. As shown in the present studies, the demonstration of the restriction is directly dependent on the dose and the relative protective activity of spleen cells. In addition, some H-2-unrestricted protection is conferred predominantly by other than immunoglobulin-negative spleen cells. Thus, the activity of Listeria-immune T cells appears to be 'absolutely' restricted and is in this respect comparable to in vivo T-cell-mediated anti-viral protection. The predominant genetic region of H-2 coding for the structures which are mainly involved in this restriction in T-cell immunity to this prototype intracellular bacterium is the I region. The specificity of Listeria-immune T cells is determined by the H-2 haplotype of the donor. Thus, F1 hybrids seem to possess at least two separable sets of T cells, each specific for one parental haplotype. As is true in the virus model, the results cannot distinguish between an altered-self or a dual recognition model of T-cell recognition to explain H-2 restriction. They are, however, compatible with the idea and I-coded cell surface structures may serve as receptors for cell-specific differentiation signals, which trigger direct or lymphokin-mediated activation of macrophages to manifest increased bactericidal capacity. The interesting parallels in self-marker recognition of T cells in the virus and intracellular bacterium systems, respectively, appear to be reasonably explained by the different types of signals transmitted by T cells to various target cells via the distinctly different self-markers employed (i.e., K or D vs I).
In vitro tolerance induction of neonatal murine B cells as a probe for the study of B-cell diversification.
Authors: Metcalf E S , Sigal N H , Klinman N R
Published: June 2004

The susceptibility to in vitro tolerance induction has been implicated as a characteristic of B cells early in their development, since DNP-reactive B cells are tolerizable only during the first days after birth, and 25% of adult bone marrow cells are tolerizable. In the present study, a modification of the in vitro splenic focus technique was utilized to determine if PC-specific B cells, by virtue of their late expression (approximately 1 wk post-parturition), also display susceptibility to tolerance induction. The results demonstrate that at 7-10 days after birth, when over 90% of the DNP-specific splenic B cells are resistant to tolerance induction, the majority of PC-specific B cells are tolerizable. These results re-emphasize tolerance susceptibility as a characteristic of developing clones, confirm the late acquisition of PC-specific B cells, and support the contention that the acquisition of the specificity repertoire is a highly ordered, specifically predetermined process which is independent of antigen-driven events.
Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages
Authors: Andersson J , Coutinho A , Melchers F
Published: June 2004

Frequencies of mitogen-reactive B cells have been determined in vitro under culture conditions which allow every growth-inducible B cell to grow and mature into a clone of Ig-secreting PFC.

The frequencies of LPS-reactive B cells in the spleen of 6- to 8-wk old mice were between 1 in 3 and 1 in 10 splenic B cells from the following inbred strains of mice: C3H/Tif; BALB/c; BALB/c ν/ν; C57BL/6J; DBA/2J; C57BL/6J x DBA/(2J)F(1); and CBA and A/J. Very similar frequencies are found for lipoprotein-reactive B cells in BALB/c, BALB/c ν/ν, C3H/Tif, and C3H/HeJ mice. No LPS-reactive cells but normal frequencies of lipoprotein-reactive cells were found in C3H/HeJ mice, genetically nonreactive to LPS. SJL mice had significantly lower frequencies of LPS- and of lipoprotein-reactive B cells (1 in approximately 30 B cells).

The number of LPS- and of lipoprotein-reactive B cells in spleen was dependent upon the age of the mouse. Newborn spleen contained approximately 10 percent of the number of reactive cells found at 6- to 8-wk of age. From there the frequencies declined again to drop below 5 percent of the maximal number at ages beyond 11 mo.

LPS-reactive B cells yielding IgM- and IgG-PFC responses could be found in mesenteric lymph nodes, bone marrow, thymus, thoracic duct, and peripheral blood of 6- to 8-wk old mice. Their frequencies were one in three to five lymph node cells, 1 in 50 to 100 bone marrow cells, one in 10(5) thymus cells, and 1 in 20 to 40 thoracic duct or peripheral blood cells.
Mutation in a new H-2-associated histocompatibility gene closely linked to H-2D.
Authors: Hansen T H , Cullen S E , Melvold R , Kohn H , Flaherty L , Sachs D H
Published: June 2004

Sequential precipitations of soluble BALB/c antigen with antisera detecting private and public H-2 specificities indicated three distinct classes of molecules of 45,000 mol wt. However, only two of these classes of molecules were detectable in antigen from the loss mutant, BALB/c-H-2db. The class of molecules, detectable in the wild-type strain but missing in the mutant, does not bear private specificities but does react with an antiserum detecting H-2 public specificities. Absorption in mutant mice of the antiserum to public specificities, left antibodies specific for the antigen detectable in BALB/c but not BALB/c-H-2db. Genetic mapping studies using this specific antiserum indicated that the antigenic loss of this mutant is in a gene which maps in or close to the H-2D region, separable from the H-2K, S, G, Qa-2, and Tla regions.
B-cell tolerance. III. Effect of papain-mediated cleavage of cell surface IgD on tolerance susceptibility of murine B cells.
Authors: Cambier J C , Vitetta E S , Kettman J R , Wetzel G M , Uhr J W
Published: June 2004

Under defined conditions, papain removes IgD from cells while leaving IgM, H-2, Ia, Lyb-2, and complement receptor intact. The effect of such treatment with papain on the induction of tolerance in murine splenic B cells was determined in an in vitro system. Treatment of the cells with papain has no effect on subsequent antibody responsiveness presumably because surface receptors regenerate before and during incubation with immunogen. Removal of increasing amounts of IgD results in increasing susceptibility of thymus-dependent responsive cells to tolerance induction. The tolerance susceptibility of thymus-independent responsive cells, which we have previously suggested are immature cells that bear only IgM, is unaffected by cleavage of IgD. If cells are incubated for 24 h after treatment with papain, cell surface IgD and tolerance resistance return. These results indicate that a surface molecule affects susceptibility of B cells to induction of tolerance and suggest that this molecule may be IgD.
Trypanosoma cruzi: modification of macrophage function during infection.
Authors: Nogueira N , Gordon S , Cohn Z
Published: June 2004

Infection of mice with Trypanosoma cruzi and subsequent intraperitoneal challenge with heat-killed trypanosomes elicits peritoneal macrophages which display in vitro microbicidal activity against trypomastigotes of T. cruzi. These cells also display other activated properties including rapid spreading, intense membrane activity, secretion of high levels of plasminogen activator, and ingestion mediated by the C3 receptor. An intravenous infection with BCG, followed by an intraperitoneal challenge with mycobacterial antigens brings about macrophages with similar properties. These criteria of macrophage activation were compared in normal and BCG- or T. cruzi-immune mice, with or without an intraperitoneal challenge with specific or unrelated antigens. Trypanocidal activity is displayed by both BCG- and T. cruzi-immune macrophages after intraperitoneal challenge with either antigen. Resident-immune macrophages from both T. cruzi- and BCG-infected mice show a trypanostatic, rather than trypanocidal activity. Macrophages from noninfected mice, challenged with the same antigens, show neither trypanostatic nor trypanocidal activity. Increased secretion of plasminogen activator shows a definite immunological specificity. Challenge with the specific antigen induces the appearance of macrophages secreting high levels of plasminogen activator, while unrelated antigens induce much smaller levels. Noninfected mice challenged with the same antigens do not display any enchancement in secretion. In contrast, increased spreading and phagocytosis mediated by the complement receptor are also displayed by cells from noninfected mice challenged with any of the agents tested.
Trypanosoma cruzi: the immunological induction of macrophage plasminogen activator requires thymus-derived lymphocytes.
Authors: Nogueira N , Gordon S , Cohn Z
Published: June 2004

In this article we describe methods in which unstimulated mouse peritoneal macrophages were induced to secrete high livels of plasminogen activator under in vitro conditions. The exposure of sensitized peritoneal or spleen cell populations from Trypanosoma cruzi-infected animals to either viable or heat-killed trypanosomes lead to the release of an inducing factor(s). Maximal levels of plasminogen activator secretion are achieved by the incubation of such factors (s) with unstimulated macrophages for 48 h. A significant increase in enzyme secretion was already observed after a 24 h incubation. The production of the inducing factor(s) by sensitized cells was immunologically specific and unrelated antigens did not stimulate the production of the factor(s) by sensitized peritoneal or spleen cell populations. The inducing factor(s) was produced by nylon-wool-fractionated spleen and peritoneal cells which had been depleted of marcrophages. Pretreatment of sensitized spleen cells with anti-theta serum and C abolished the production of the activating factor(s). The active supernatant fluids were able to induce secretion of macrophage plasminogen activator across H-2 barriers. Attempts to induce trypanocidal activity in unstimulated macrophages have not been successful.
Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG.
Authors: Moretta L , Webb S R , Grossi C E , Lydyard P M , Cooper M D
Published: June 2004

Subpopulations of thymus-derived T lymphocytes bearing receptors for either IgM or IgG molecules were isolated from human peripheral blood. Those with receptors for IgM (T.M) provided help in a cell dose-dependent fashion for the pokeweed mitogen-induced differentiation of B lymphocytes in vitro, whereas cells with receptors for IgG (T.G) did not. T.G cells, on the hand, efficiently suppressed the differentiation and proliferation of B cells in the pokeweed system in the presence of helper T.M cells. This suppressive activity of T.G cells required prior interaction of the T.G cells with immune complexes. The helper activity of T.M cells was relatively radioresistant while the suppressor activity of T.G cells was radiosensitive. The results indicate that helper and suppressor functions of human T lymphocytes in this model system are mediated by different subpopulations of T cells which can be distinguished by their ability to bind IgM or IgG immune complexes, respectively.
Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection
Authors: Halstead SB , O'Rourke EJ , Allison AC
Published: June 2004

Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 μg/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.
Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution.
Authors: Pangburn M K , Schreiber R D , Müller-Eberhard H J
Published: June 2004

The complement regulatory enzyme, C3b inactivator (C3bINA), has been purified from human serum by affinity chromatography on an anti-C3bINA Sepharose column. Subsequent chromatography on DEAE-cellulose and removal of IgG with anti-IgG Sepharose resulted in a product which was found to be homogeneous by polyacrylamide gel electrophoresis at pH 8.9 and by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The molecule is composed of two disulfide bonded polypeptide chains with mol wt of 50,000 and 38,000 daltons. Human CobINA was found to be a glycoprotein containing at least 10.7% carbohydrate and to have a normal serum concentration of 34 +/- 7 mug/ml (mean +/- 1 SD). Highly purified C3bINA cleaved neither free C3b nor free C4b if trace amounts of contaminating beta1H were removed from these proteins with anti-beta1H Sepharose. However, in the presence of highly purified beta1H and C3bINA, both C3bIna, both C3b and C4b were cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their cleaved. Incubation of native C3 or C4 with C3bINA and beta1H had no effect on their structure. The action of C3bINA and beta1H on C3b produced two fragments of the alpha1-chain which did not dissociate without reduction of the molecule. These fragments have mol wt of 67,000 and 40,000 daltons. The action of C3bINA and beta1H on C4b resulted in cleavage of the alpha'-chain giving rise to the 150,000-dalton C4c and the 49,000-dalton C4d fragments which dissociated without reduction. To produce from C3b the immunochemically defined C3c and C3d, fragments, the action of an additional serum enzyme appears to be required, the effect of which can be mimicked by trypsin.
The I-J subregion codes for determinants on suppressor factor(s) which limit the contact sensitivity response to picryl chloride
Authors: Greene MI , Pierres A , Dorf ME , Benacerraf B
Published: June 2004

The cell-mediated immune reactivity (CMI) of mice to contact chemicals such as picryl chloride (PCI) is influenced by thymus-derived suppressor T lymphocytes (1,2). The development of these suppressor T lymphocytes is stimulated by the intravenous administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Zembala and Asherson have further demonstrated that a specific suppressor factor(s) can be detected in the supernates of cultured suppressor T cells. This factor suppresses the transfer of contact sensitivity (CS) to PCl (1,2). In experiments reported elsewhere (3), we have shown that the PCl suppressor supernates of Zembala and Asherson can also suppress the development of contact sensitivity to PCl. The immunochemical analysis of suppressor factor (SF) operative in the CS response to PCl has revealed many similar properties (3) to other suppressive moieties functioning to limit the plaque-forming cell (PFC) response to dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) as well as the strict antigen specificity of each respective suppressive factor, suggested that there might be a common origin of these substances. Indeed, in each case these respective factors were found to bear determinants controlled by the H-2 gene complex (4,5).

Recently, in selected systems, the I-J subregion has been found to code for the Ia determinants present on suppressor cells (6) and suppressor factors (4,5). In accord with these findings, we report that antigen-specific SF which limit the CS response to PCl bear I-J determinants, implying that analogous suppressive regulatory mechanisms in CMI as well as antibody responses may be determined by genes of one subregion of the H-2 complex.
Ontogeny of Ia and IgD on IgM-bearing B lymphocytes in mice.
Authors: Kearney J F , Cooper M D , Klein J , Abney E R , Parkhouse R M , Lawton A R
Published: June 2004

We used immunofluorescence to examine the developmental relationship of Ia and IgD on B cells. Pre-B cells in fetal liver did not express Ia. Only very few surface IgM-positive (sIgM+) B cells in fetal spleen were found to be Ia+ and were weakly stained for Ia. After birth there was a linear increase in the proportion of sIgM+ spleen cells which expressed Ia, reaching 95% by 9 days. Adult bone marrow also contains a sizeable proportion of sIgM+ Ia- cells. Unstimulated cells from fetal or newborn liver and spleen expressed Ia at the same rate in culture. Anti-Ia antisera suppressed the LPS-induced differentiation of IgM and IgG plasma cells in cultures of neonatal lymphocytes. Ia was also detected on IgM and IgG plasma cells in vitro suggesting that lipopolysaccharide (LPS)-stimulated B cells by may express Ia antigens, induced by LPS, or appearing as part of normal differentiation. IgD did not appear on sIgM+ cells until 3 days of age and then rose slowly to reach adult levels later than Ia antigens.
Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts.
Authors: Slavin S , Strober S , Fuks Z , Kaplan H S
Published: June 2004

BALB/c mice were treated with fractionated high dose (3,400 rads) total lymphoid irradiation (TLI), and given semiallogeneic (BALB/c x C57BL/Ka) or allogeneic (C57BL/Ka) bone marrow and/or skin allografts. TLI alone prolonged the mean survival time (m.s.t.) of C57BL/Ka skin grafts to 49.1 days (control, 10.7 days). Shielding of the thymus during TLI produced only a slight increase in graft survival (m.s.t., 19 days). TLI combined with splenectomy was no more effective than TLI alone. Infusion of 10(7) semiallogeneic or allogeneic bone marrow cells after TLI produced stable chimeras in 7/8 and 8/15 recipients, respectively. Chimeras were specifically tolerant to donor tissues, since C57BL/Ka skin grafts were accepted for more than 250 days, but third-party (C3H/He) skin grafts were rejected rapidly. In addition, chimeric lymphocytes responded to C3H/He and C3H. Q but not to C57BL/Ka cells in the one-way mixed leukocyte reactions. BALB/c C57BL/Ka chimeras showed no clinical evidence of graft vs. host disease. These findings may have application of clinical organ transplantation, since (a) the recipient treatment (TLI) has already been shown to be safe in humans, (b) donors and recipients can be completely allogeneic, and (c) bone marrow and skin graft survival was permanent (greater than 250 days).
Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants.
Authors: Claman H N , Miller S D , Sy M S
Published: June 2004

Genetic restrictions in generation and expression of hapten-specific suppressor cells for contact sensitivity were found. Dinitrophenol- (DNP) or trinitrophenol-modified mouse spleen cells (SC) induced suppressors in donors able to transfer suppression to normal recipients. When allogeneic DNP-SC were injected into BALB/c mice, cells were generated which were suppressive only in the allogeneic strain providing the DNP-SC. In contrast, when DNP-BALB/c-SC were injected into BALB/c mice, suppressors were generated which were active both in BALB/c and in allogeneic mice (e.g., CBA). This apparent absence of syngeneic major histocompability complex restriction may be explained by cross reactive T-cell receptors which are VH gene products.
Ly phenotype and mechanism of action of mouse neonatal suppressor T cells.
Authors: Mosier D E , Mathieson B J , Campbell P S
Published: June 2004

Neonatal suppressor T cells were isolated from the thymuses of 10- to 14-day old BDF mice infected at birth with mouse thymic virus. Such cells were enriched for suppressive activity directed against antibody formation by adult B cells and represented a relatively homogenous population of outer cortical cells. Their surface antigen phenotype was found to be: Ly 1+, Ly 2+, TL+, Thy 1+, and H-2+. The cells were larger and contained more DNA than thymocytes from age-matched controls. These findings identify neonatal suppressor T cells as a unique subpopulation separate from most inducible suppressor cells in the adult mouse. The mechanism of action of neonatal suppressor T cells seems to be a reduction in the number of B cells initially triggered by antigen.
Enrichment of antigen-specific B lymphocytes by the direct removal of B cells not bearing specificity for the antigen.
Authors: Walker S M , Meinke G C , Weigle W O
Published: June 2004

Antigen-specific B cells (ASC) were purified from other B cells by prior incubation with specific antigen followed by rosetting with erythrocytes conjugated with anti-mouse Ig and sedimenting on Ficoll-Isopaque. This procedure allowed the removal of most of the B cells, while those speicifc for the antigen used in incubation were retained. Relative to the B-cell content, ASC were enriched 64- to 132-fold. The method is highly specific in that B cells primed to two different antigens, turkey gamma globulin and sheep erythrocytes, could be separated from each other. The advantages of this indirect purification procedure over purification procedures which obtain ASC directly are the simplicity of obtaining the ASC and the ability of the ASC of respond to antigen without the addition of other cells.