bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen-initiated B lymphocyte differentiation. XX. Colony-forming B lymphocytes are not identical with the intermediate, "pre-progenitor" subset of primary or secondary B cells.
Authors: Jennings G , Shortman K
Published: December 2022

The surface immunoglobulin isotype and the cell cycle status of B lymphocyte agar-colony-forming cells (BL-CFC) were studied in order to test a hypothesis, based on their culture behavior, that they represent a mixture of virgin and memory "intermediate" or "pre-progenitor" B cells. If so, BL-CFC would be equivalent to the minor subset of B cells initiating adoptive immune responses. Most BL-CFC were found to be s-IgD+, whereas most progenitors of primary or secondary adoptive responses were s-IgD-. An intense nonspecific stimulus, in the form of horse erythrocytes injected i.p., failed to throw BL-CFC into cell cycle, as judged by hydroxyurea suicide experiments, whereas the progenitors of adoptive responses were thrown into cell cycle. It was concluded that BL-CFC as a whole were not "pre-progenitor" B cells, but more closely resembled the typical "direct progenitor" B cell. Some data derived from unprimed animals, namely, the level of dividing BL-CFC as assessed by hydroxyurea killing and sedimentation velocity distribution, together with the special sensitivity of even nondividing BL-CFC to killing by 3H-TdR, suggested that the agar culture system might select more activated B cells as colony formers.
Immunosuppressive effect of mouse serum lipoproteins. II. In vivo studies.
Authors: Hsu K H , Hiramoto R N , Ghanta V K
Published: December 2022

Normal mouse serum lipoproteins suppress a number of immunologic functions, such as mitogen stimulation, primary immune response, and allograft rejection in vivo. The effects of one class of lipoproteins, high density lipoprotein (HDL), were investigated after i.v. administration. Maximum suppression of spleen and peripheral blood lymphocyte (PBL) mitogen stimulation occurred when HDL was administered up to 8 hr before testing. Spleen cells remained suppressed 48 hr after injection, while PBL regained most of their activities. Injection of HDL 24 hr after sheep red blood cell (SRBC) immunization was as effective as giving HDL 8 hr before SRBC in suppressing primary immune response to SRBC. Induction of T cell allograft immunity was also suppressed by the injection of HDL.
Expression on normal lymphocytes of two cell surface antigens, XenCSA and GIX, related to the major glycoproteins (gp70) of murine leukemia viruses.
Authors: Morse H C , Taylor B A , Kozak C A , Chused T M , Sharrow S O , Hartley J W , Stockert E
Published: December 2022

XenCSA and GIX are two cell surface antigens related to the major envelope glycoproteins (gp70) of murine leukemia viruses. The levels of expression of these gp70 determinants were assessed in 36 recombinant inbred mouse strains and selected backcrosses derived from crosses between C57BL/6 with DBA/2 and C3H/He. These two antigens segregated in backcross mice and showed a different strain distribution pattern among the recombinant inbred mice, demonstrating that XenCSA and GIX are distinct genetic markers for different endogenous gp70 sequences. It was also shown that independent sets of gene regulate the expression of XenCSA and GIX.
Abnormal migration of T lymphocyte clones.
Authors: Dailey M O , Fathman C G , Butcher E C , Pillemer E , Weissman I
Published: December 2022

Several in vitro T cell clones were markedly deficient in their ability to home to peripheral lymphoid tissue. This was found for an alloreactive noncytolytic clone, a soluble antigen- (KLH)specific line, and cytotoxic clones specific for allogeneic cells and for Abelson virus-induced lymphoma cells. This abnormal circulation pattern was probably caused by the lack of the receptors of the lymphocytes for high endothelial venules (HEV), as implied by the lack of binding of these T cells to HEV in frozen sections of mouse lymph node and Peyer's patches. The loss of surface receptors that are necessary for normal lymphocyte migration may thereby alter the in vivo function of adoptively transferred T cells.
Induction of autoimmune phenomena in normal mice treated with natural thymocytotoxic autoantibody.
Authors: Nakanishi A , Imai Y , Nakano T , Osawa T
Published: December 2022

Natural thymocytotoxic autoantibody (NTA) developed spontaneously in New Zealand Black (NZB) mice consists of two autoantibodies in terms of target cell specificity. One of the autoantibodies, NTA-2, is strongly cytotoxic only against desialized lymphocytes, whereas the other one, NTA-1, is cytotoxic against both intact thymocytes and asialolymphocytes. To study the pathogenic role of NTA in murine autoimmunity, DBA/2 mice were injected every other day with affinity-purified NTA (NTA-1, NTA-2). Control mice received normal mice sera (NMS) or saline. After 20 days of treatment, spleen cells from DBA/2 mice treated with NTA-1 or NTA-2 showed a significant increase in the number of anti-ssDNA plaque-forming cells and IgM-producing cells. Sera from NTA-treated mice showed greater DNA binding than sera from control mice did. The levels of proteinuria were moderately increased in NTA-2-treated mice. Con A responsiveness of thymocytes was markedly reduced in NTA-2-treated mice. On the other hand, Con A-activated spleen cells from both control and NTA-treated mice equally suppressed anti-SRBC antibody production in vitro, suggesting that NTA treatment didn't affect the direct precursors of suppressor T cells. Finally, prior absorption of NTA-1 by thymocytes prevented its ability to induce anti-DNA antibodies; however, prior absorption of NTA-2 by thymocytes didn't affect its activity.
Sensitization of human lymphocytes in vitro: genetic restriction of secondary T cell responses is dictated by the HLA-DR phenotype of antigen-presenting cells.
Authors: Ford D M , Hamblin A , Burger D R
Published: December 2022

Antigen-specific proliferation of human T cells sensitized in vitro was found to be macrophage dependent and HLA-DR restricted. Primary sensitization or secondary restimulation did not occur in the absence of antigen-presenting macrophages. The macrophage requirement for secondary restimulation was restricted by specificities shared between macrophages used for primary sensitization and T cells of the HLA-DR locus. Moreover, the magnitude of the response to antigen appeared to be related to the number of HLA-DR haplotypes shared between antigen-presenting cells in primary and secondary cultures. This observation could be attributed to a clonal response of the T cells with respect to HLA-DR on macrophages. Using HLA-DR 3/5 heterozygous KLH-primed T cells, elimination of cells responsive to antigen-pulsed HLA-DR 3/3 macrophages by thymidine suicide techniques left intact responsiveness to antigen-pulsed HLA-DR 5/5 macrophages. Tp determine whether the genetic restriction was dictated by the HLA-DR genotype of the responding lymphocytes or the HLA-DR phenotype of the responding lymphocytes or the HLA-DR phenotype of the antigen-pulsed macrophages, allogeneic macrophages were used to present antigen in primary culture. After elimination of alloreactive cells, proliferation in secondary cultures was found to be dependent on HLA-DR determinants shared between macrophages used for secondary restimulation and those used in primary sensitization, regardless of the HLA-DR genotype of the responding T lymphocytes.
Interleukin 2 regulates immune interferon (IFN gamma) production by normal and suppressor cell cultures.
Authors: Torres B A , Farrar W L , Johnson H M
Published: December 2022

A Lyt-2+ lymphocyte is responsible for immune interferon (IFN gamma) production in mitogen-stimulated mouse spleen cell cultures. A Lyt-1+ helper cell is required for the induction of IFN gamma. Interleukin 2 (IL 2) can specifically replace the Lyt 1 cell requirement. IL 2 will also abrogate suppressor cell inhibition of IFN gamma production. IFN gamma production appears to be regulated by a dynamic interaction between helper cells (source of IL 2), suppressor cells (absorption of IL 2?) and IFN gammna-producer cells.
Release of leukotrienes from guinea pig lung stimulated by C5ades Arg anaphylatoxin.
Authors: Stimler N P , Bach M K , Bloor C M , Hugli T E
Published: December 2022

The complement anaphylatoxins C5a and C5Ades Arg contract guinea pig peripheral airway preparations and trachea by a mechanism largely independent of histamine release. In trachea the contractions are inhibited by FPL 55712, a relatively specific inhibitor of slow-reacting substance of anaphylaxis (SRS-A). SRS-A is now known to be a mixture of leukotrienes C4, D4, and E4 (LTC4, LTD4, LTE4). These data suggest that C5-derived anaphylatoxins stimulate production and release of leukotrienes in pulmonary tissues. To define these observations more precisely, fragments of guinea pig lung were incubated with porcine C5ades Arg, and the supernatant fluids were analyzed for leukotrienes by using both pharmacologic and chemical methods. In addition to histamine, a smooth muscle contracting activity characteristic of SRS-A was released from C5a-treated lung preparations. The contractile substance was identified as a leukotriene based on: 1) the characteristic contraction of guinea pig ileum, 2) inhibition of the contractile activity by FPL 55712, 3) enhanced release of activity in the presence of indomethacin or L-cysteine, 4) chromatographic behavior of ethanol-extracted active material on Amberlite XAD-7 resin, and 5) cochromatography of the active material on reverse-phase, high performance liquid chromatography with standard LTD4. We therefore concluded the humoral factor C5ades Arg induces a leukotriene release reaction in guinea pig lung tissue. This particular response of pulmonary tissue to anaphylatoxin has not been appreciated previously as an immediate effect of complement activation on the pathophysiology of the lung.
Modulation of chronic lymphocytic leukemia cells by phorbol ester: increase in Ia expression, IgM secretion and MLR stimulatory capacity.
Authors: Okamura J , Letarte M , Stein L D , Sigal N H , Gelfand E W
Published: December 2022

When cultured with 12-O-tetradecanoylphorbol 13-acetate (TPA) at a concentration of 1.6 X 10(-7) M, chronic lymphocytic leukemia (CLL) cells differentiated into mature cells of B lineage and increased their expression of surface Ia antigens when compared with cells cultured in the absence of TPA. Concurrently, TPA enhanced the ability of CLL cells to stimulate in a mixed lymphocyte reaction (MLR). The events induced in vitro by TPA that are characteristic of B cell maturation included morphologic changes, reduction in surface immunoglobulin (Ig), appearance of cytoplasmic Ig, and secretion of IgM. The increase in Ia expression and the enhanced capacity to stimulate in an MLR after incubation with TPA might also be associated with maturation of the CLL cells. The changes induced in vitro by TPA in neoplastic B cells provide new information concerning the terminal events in normal B cell differentiation.
The binding of staphylococcal protein A by the sera of different animal species.
Authors: Richman D D , Cleveland P H , Oxman M N , Johnson K M
Published: December 2022

The capacity of purified immunoglobulin or serum to bind (125I)-labeled staphylococcal protein A (SPA) was measured by means of an immunofiltration assay that facilitated the examination of large numbers of sera and required only a minute quantity of each. Sera from 80 species, including humans, laboratory animals, domestic animals, and a variety of African mammals were examined. A wide interspecies variation in the SPA-binding capacity of serum immunoglobulins was confirmed. Only small variations were observed among individuals within the same species with one notable exception. A greater than 10,000-fold variation in SPA-binding capacity was observed among sera from nine goats. Interspecies differences in serum SPA-binding capacity correlated well with taxonomic differences, and the serum SPA-binding capacity correlated well with taxonomic differences, and the serum SPA-binding capacities of African mammals corresponded closely to those of their more common relatives. The sensitivity of antibody detection by indirect (125I)SPA immunoassay was shown to be determined mostly by the SPA-binding capacity of the serum examined. The titer of antibody to influenza A/Texas/1/77(H3N2) virus in sera from several different species, when measured by (125I)SPA immunofiltration assay, was directly proportional to the SPA-binding capacity of the serum and was not proportional to the hemagglutination inhibition titer. An (125I)SPA immunofiltration assay for antibody to Lassa virus in the serum of Mastomys natalensis (which binds SPA only one-thousandth as well as human serum) was at least as sensitive as the standard fluorescent antibody assay.
SAA suppression of immune response in vitro: evidence for an effect on T cell-macrophage interaction.
Authors: Aldo-Benson M A , Benson M D
Published: December 2022

SAA has been shown previously to inhibit the in vitro antibody response of normal murine spleen cells to SRBC. This effect is nonspecific but does not directly suppress B cells. To evaluate the mechanisms of this suppression, the in vitro antibody response to SRBC was studied using cells from cytoxan-treated mice. No evidence for preformed suppressor cells was found. Also, preincubation of normal cells with SAA failed to reveal evidence for the generation of suppressor cells in vitro. The addition of 2-mercaptoethanol to cultures completely reversed the suppression caused by SAA. Addition of either normal T cells or normal macrophages to cultures partially reversed suppression caused by SAA, but only a combination of T cells and macrophages could completely reverse the suppression. These data are consistent with an effect of SAA on macrophage-T cell interaction in the generation of the immune response to T-dependent antigen. No evidence for the participation of suppressor cells as has been demonstrated for alpha-fetoprotein was found.
Induction of anterior chamber-associated immune deviation (ACAID) by allogeneic intraocular tumors does not require splenic metastases.
Authors: Niederkorn J Y , Streilein J W
Published: December 2022

Anterior chamber-associated immune deviation (ACAID), induced by intracameral injection of allogeneic tumor cells, is expressed in three distinct ways: 1) progressive growth of intraocular tumors, 2) specific suppression of systemic allograft immunity, and 3) transient growth of allogeneic tumors injected subcutaneously. Induction of ACAID requires that alloantigen presentation occur via the anterior chamber; injection by other routes failed to elicit this phenomenon. Antigenic material must remain in the anatomically intact eye for at least 10 days; removal of the injected dye before this time prevented the establishment of ACAID. The similar temporal requirement for an anatomically intact spleen confirms the validity of the concept of a camero-splenic axis for processing of intracamerally injected alloantigens. Deployment of an alternate model of ACAID, using LP/J mice injected intracamerally with B16F10 melanoma, showed the antigen-specific inductive signal for ACAID (transmitted via the camero-splenic axis) was not in the form of viable alloantigen-bearing tumor cells that metastasize to the spleen. B16F10 melanoma cells were never found in the spleens or any other extraocular sites after intracameral injection, despite the fact these mice manifested ACAID and harbored enormous ocular tumors. The data emphasize that intraocular processing of antigens is a unique and dynamic phenomenon with significant, systemic immunologic consequences.
An erythrocyte and serum antigen with a specificity antithetical to the mouse C4 associated H-2.7 antigen.
Authors: Passmore H C
Published: December 2022

Repeated immunization of intra-H-2 recombinant strain A.TBR16 with lymphoid tissue from strain A.TBR13 produced an antiserum that agglutinated the erythrocytes from inbred strains of mice carrying the b, d, r, q, u, wr7, w13, w17, w19, and w21 haplotypes of the H-2 complex. The antiserum was negative with erythrocytes of strains carrying the haplotypes f, j, k, p, and s. This pattern of reactivity among fifteen H-2 haplotypes is unlike the strain distribution for any known H-2 erythrocyte antigen, and is exactly antithetical to the S region-controlled H-2.7 antigen. An examination of 12 intra-H-2 recombinant haplotypes mapped the genetic determinant controlling the new antigen to the IC or S regions of the H-2 complex. In addition, hemagglutination inhibition studies revealed the antigen was also expressed in serum and plasma. The serologic, genetic, and tissue distribution data suggest the gene controlling the newly defined antigen is allelic to the gene controlling the H-2.7 antigen.
Subcellular distribution of particle-associated antigens in Trypanosoma rhodesiense.
Authors: McLaughlin J
Published: December 2022

Bloodstream forms of the African trypanosome Trypanosoma rhodesiense were subjected to analytic cell fractionation procedures using isopycnic sucrose gradient centrifugation. The fractions obtained were analyzed using fused rocket immunoelectrophoresis, which revealed the most antigenic components to be associated with particles sedimenting between density increments of 1.10 to 1.15 and 1.20 and 1.22. From the distribution of various marker enzymes and the fluorogenic label fluorescamine, these particle populations were identified as derived from flagella pocket and surface membrane, respectively. Crossed immunoelectrophoresis of postulated flagella pocket and surface membrane fractions demonstrated at least seven and 10 distinct antigens, respectively, with only limited cross-reactivity. On the basis of crossed affini-immunoelectrophoresis four to five of each of these membrane antigens were glycoproteins, being precipitated in a concanavalin A-containing gel. Of the various detergent treatments used, it was found that optimum extraction of these glycoprotein antigens was achieved using the zwitterionic detergent Zwittergent 3-12 (0.1%) in the presence of 0.4% Triton X-100. Fused rocket immunoelectrophoresis also revealed a single prominent antigen associated with a particle population having an equilibrium density of approximately 1.180, which was identified as lysosomal from the distribution of marker enzymes. Other intracellular sites were not significantly antigenic.
Delineation of four antigenic sites on a paramyxovirus glycoprotein via which monoclonal antibodies mediate distinct antiviral activities.
Authors: Yewdell J , Gerhard W
Published: December 2022

Six hybridoma antibodies specific for the hemagglutinin-neuraminidase (HN) molecule of the parainfluenza type 1 virus strain 6/94 were used to demonstrate the existence of four distinct antigenic sites on the HN molecule. Three of the sites (A, B-C, D) are topologically nonoverlapping, because antibodies to these sites bind noncompetitively to the HN molecule. Two sites (B, C) are operationally nonoverlapping, because mutations in site B do not detectably modify the antigenic site C. Although antibodies to each site had similar potencies (activity per microgram of antibody) in hemagglutination inhibition tests, antibodies to sites A and C or D differed approximately 100-fold in their potency to neutralize virus. Also, the antibody to site A strongly inhibited viral neuraminidase activity, whereas antibodies to sites C and D (and to a lesser extent to site B) enhanced the neuraminidase activity. Lastly, only antibodies to sites C and D formed precipitates in Ouchterlony double diffusion against detergent-disrupted virus. Because all six anti-HN antibodies are of IgG isotype and exhibited similar avidity for HN, these findings suggest that the ability of anti-HN antibodies to interact with the viral protein and to alter viral functions is largely dependent on their fine specificity.
The presence of sialic acid on two related bacterial polysaccharides determines the site of the primary immune response and the effect of complement depletion on the response in mice.
Authors: Markham R B , Nicholson-Weller A , Schiffman G , Kasper D L
Published: December 2022

We have examined the antibody responses in mice to two structurally similar antigens: the capsular polysaccharide of type 3 group B streptococci (sssGBS 3) and the capsular polysaccharide of type 14 pneumococci (sssPn 14), which differ only in the presence of a terminal sialic acid on the side chain of the former. The cells that produce antibody to the nonsialated antigen (sssPn 14) reside in the spleen, whereas the cells that produce antibody to the sialated antigen (sssGBS 3) do not. Cobra venom factor treatment of the mice before immunization abrogates the antibody response to the nonsialated antigen, but does not affect the response to the sialated antigen.
Soluble bacterial antigen induces specific helper and cytotoxic responses by human lymphocytes in vitro.
Authors: Hank J A , Sondel P M
Published: December 2022

Fresh human T lymphocytes respond proliferatively to soluble antigens, such as PPD, provided the cell donor has been immunized to those antigens in vivo. This proliferative response requires the addition of antigen-presenting cells bearing autologous HLA-D antigens. This report demonstrates that the proliferative response to PPD activates a collaborative response that aids in the activation of alloreactive cytotoxic T cells (Tc). Furthermore, the proliferative response to "soluble" PPD alone activates a population of Tc specifically able to destroy autologous target cells passively labeled with PPD. Allogeneic PPD-labeled targets are killed less effectively. This PPD-specific cytotoxicity is not inhibited by soluble PPD, but is competitively inhibited by PPD-labeled autologous cells. Thus, in vitro stimulation with "soluble" bacterial antigen activates both helper and cytotoxic recognition of antigen-altered self by a mechanism comparable to the recognition of viral or hapten-altered cells.
Ia antigen expression and antigen-presenting function by macrophages isolated from hypersensitivity granulomas.
Authors: Stadecker M J , Wyler D J , Wright J A
Published: December 2022

Macrophages were isolated from granulomas elicited in the liver by the eggs of the trematode Schistosoma mansoni. They were analyzed for the expression of determinants encoded by the I-A subregion of the major histocompatibility complex and for their ability to present antigen in a T cell proliferation assay. Seventy-five to 81% of the macrophages were found to bear I-A antigens after 24 hr in culture; they also were shown to be effective in carrying out antigen-presenting function. Subsequent in vitro cultivation for up to 4 days demonstrated a progressive loss of I-A molecules, which correlated with a corresponding reduction in antigen-presenting capability. The latter was antigen-specific, blocked by monoclonal antibody directed against I-A, and abrogated after depletion of I-A-positive macrophages. Populations of macrophages from hepatic egg granulomas were richer in I-A-positive cells, and were more effective in terms of antigen-presenting capability compared to those obtained from foreign body-type granulomas. These observations suggest a central role for macrophages from infectious granulomas in the induction and maintenance of immunity and hypersensitivity.
Assays for the Sm and RNP autoantigens: the requirement for RNA and influence of the tissue source.
Authors: White P J , Billings P B , Hoch S O
Published: December 2022

The disease systemic lupus erythematosus is characterized by antibodies directed against two nuclear antigens, designated Sm and RNP. The two antigens from any one tissue can be distinguished on the basis of the polypeptides recognized by anti-Sm and anti-RNP specific sera. Multiple polypeptides were associated with RNP isolated from rabbit thymus. To determine if these polypeptides were species-specific, a comparison was made of this antigen among different mammalian species. We report that the native RNP antigen has a m.w. of 70,000 and is readily susceptible to proteolysis generating smaller polypeptides that still retain antigenicity. Such an analysis also demonstrated multiple Sm-specific polypeptides, including species of 13,000 and 29,000 m.w. Because the immunoreactive species are protein in nature, the role of RNA for the detection of Sm and RNP by assay procedures such as immunodiffusion and counterimmunoelectrophoresis was examined. RNP, while still antigenically active, becomes insoluble after RNAse treatment; Sm remains largely soluble after such treatment. Both antigens can be reconstituted from their separated protein and RNA moieties with restoration of precipitin reactivity.
Relationship between the rearrangement of immunoglobulin genes, the appearance of a B lymphocyte antigen, and immunoglobulin synthesis in murine pre-B cell lines.
Authors: Sugiyama H , Akira S , Yoshida N , Kishimoto S , Yamamura Y , Kincade P , Honjo T , Kishimoto T
Published: December 2022

Eighteen Abelson virus-transformed immature B cell lines were established and immunoglobulin biosynthesis, expression of a B lymphocyte antigen detected by a monoclonal antibody, and rearrangement of immunoglobulin genes in these cell lines were studied. Only one cell line (A1) synthesized micro-chains but no light chains, and the other cell lines synthesized no detectable immunoglobulins. None of the cell lines established had detectable membrane-associated IgM. Fifteen cell lines expressed a B lymphocyte antigen on their cell surfaces. In three cell lines, however, the majority (greater than 99%) of cells did not express this antigen. Heavy chain genes were rearranged on both chromosomes in all the cell lines, although one heavy chain gene was deleted in three cell lines. In 12 of 18 cell lines, one or both kappa-chain genes were rearranged. In six cell lines, however, both kappa-chain genes remained in embryonic form; lambda-chain genes were in embryonic form in all the cell lines. These results suggested the hierarchy of Ig gene rearrangements, beginning with mu and proceeding to kappa and then to lambda. JH rearrangement was also shown to precede the appearance of a B lymphocyte antigen. In three cell lines (A1-A3), which were considered subclones derived from a single common precursor, it was suggested that one rearranged JH gene was functional, and the other was nonfunctional, indicating that allelic exclusion already operated in pre-B cells.
Dihydrotestosterone and estradiol deplete corticosensitive thymocytes lacking in receptors for these hormones.
Authors: Barr I G , Khalid B A , Pearce P , Toh B H , Bartlett P F , Scollay R G , Funder J W
Published: December 2022

The sex steroids dihydrotestosterone (DHT) and estradiol (E2), were found to deplete the same cortical population of thymocytes as the glucocorticoid dexamethasone (DM) in intact and in adrenalectomized, castrated mice. Although receptors for DM were demonstrated in this cortical population, none were found for E2 or DHT. We suggest that the sex steroids bind to other thymic elements, possibly thymic reticular epithelial cells, which may in turn act secondarily on cortical thymocytes, or their precursors within the thymus.
Presence of auto-anti-idiotypic antibody during the normal human immune response to tetanus toxoid antigen.
Authors: Geha R S
Published: December 2022

Auto-anti-idiotypic antibodies were searched for in the serum of two individuals who received booster immunization with tetanus toxoid (TT) antigen. IgG from serial bleeds obtained for 4 mo after immunization was studied a) for its capacity to specifically bind 125I IgG F(ab')2 anti-TT prepared from serum obtained 7 and 10 days post-booster immunization, and b) for its capacity (after its absorption with TT) to specifically inhibit the binding of 125I-radiolabeled TT to IgG obtained 7 and 10 days post-immunization and designated "peak IgG." In both individuals studied, auto-anti-Id IgG were detected in both assays as early as 2 wk post-booster immunization and remained detectable throughout the study period. Evidence for modulation of idiotypic expression on IgG F(ab')2 anti-TT after booster immunization with TT was obtained by studying a) the capacity of serial IgG samples to inhibit the binding of 125I-IgG F(ab')2 anti-TT to rabbit anti-Id antibody raised against the IgG F(ab')2 anti-TT, and b) the capacity of the rabbit anti-Id to specifically inhibit the binding of 125I-TT to serial samples of serum IgG. Both assays indicated that some idiotypic determinants present on anti-TT obtained before and shortly after booster immunization were expressed to a much lesser extent 2 wk and beyond after immunization. The decrease in the expression of these determinants coincided with the appearance of auto-anti-Id antibody and remained evident throughout the 4-mo study period. The results obtained indicate that auto-anti-Id antibodies arise in normal human subjects after a secondary challenge with antigen and suggest that these antibodies may play a role in the modulation of idiotypic expression that is observed after booster immunization with antigen.
Map position of Igh-Oxa gene within the Igh region of the DBA/2 mouse strain.
Authors: Pelkonen J , Karjalainen K , Mäkelä O , Taylor B A
Published: December 2022

Mice of 23 BXD recombinant inbred strains derived from the cross of C57BL/6J and DBA/2J were typed for the presence of a public idiotype found in the antibodies against the hapten phenyloxazolone (phOx) produced by DBA/2 mice. The marker is under the control of an immunoglobulin heavy-chain variable region gene, Igh-Ox. Eleven out of the 23 BXK strains shared the public idiotype with the DBA/2 progenitor, while 12 other BXD strains were negative, like the C57BL/6 progenitor. The Igh-Ox marker was inherited concordantly with allotype in all BXD strains except BXD-27, which carries the Igh-1c allotype of DBA/2 but lacks the Igh-Ox idiotype. The Igh-Ox marker was inherited concordantly with 4 other Igh-V markers (Igh-Np, Igh-Nb, Igh-Bgl, and Igh-Gte) in all BXD strains except BXD-20, which has the DBA/2 alleles at Igh-1 and Igh-Ox but resembles C57BL/6 at the other 4 markers. On the basis of these results the Igh-Ox marker is tentatively placed between Igh-C and the rest of the Igh-V markers.
Arrangement of lambda light chain genes in mutant clones of the MOPC 315 mouse myeloma cells.
Authors: Hozumi N , Wu G , Murialdo H , Baumal R , Mosmann T , Winberry L , Marks A
Published: December 2022

The synthesis of lambda light chains and the arrangement of the lambda-chain genes was examined in cells of the mouse myeloma MOPC 315, which is an alpha lambda 2 producer, and in several mutants derived from it. The mutants produce lambda 2 chains only (MOPC 315.26, MOPC 315.34, and MOPC 315.37) or fail to produce alpha and lambda 2 chains (MOPC 315.25 and MOPC 315.36). Messenger RNA from the lambda 2 chain-producing cells directed the synthesis of a lambda 2 chain precursor and a fragment of the lambda 1 chain (lambda 1 F) in a wheat embryo cellfree system, whereas mRNA from the cells that do not produce lambda 2 chains directed the synthesis of lambda 1 F only. DNA from the parental MOPC 315 cells and from the lambda 2 chain-producing cells contained discrete EcoRI restriction fragments coding for rearranged lambda 1 and lambda 23 chain genes and their respective germ-line V and J-C regions. DNA from the no-Ig-producing cells contained fragments coding for the rearranged lambda 1 chain gene and the germ-line V lambda 2 region, but it lacked the sequences coding for the rearranged lambda 2 chain gene and the germ-line V lambda 1 and J-C lambda 1 regions. These results suggest that rearrangements of the lambda 1 and lambda 2 chain genes occur on different chromosomes in MOPC 315 cells and imply that rearrangements of the lambda 1 and lambda 2 chain genes on the same chromosome may be mutually exclusive.
Genetics of cell interactions in aged mice: age-related decline in capacity of parental cells or environment to induce allogeneic effects on F1 lymphocytes.
Authors: Zuberi R I , Katz D H
Published: December 2022

In order to ascertain whether the process of aging would affect various aspects of genetic control of cell-cell interactions in mice, studies were initiated to examine the capacities of lymphoid cells and host lymphoid tissues of parental mice of varying ages to induce allogeneic effects of primed lymphocytes of young F1 donor origin. These studies demonstrate that with increasing age, both parental cells and parental environment gradually lose the capacity to influence antibody responses via the allogeneic effect. This age-related decline in induction of allogeneic effects could be attributed to 1) dysfunction or loss of allogeneic effect-inducing cells from lymphoid populations of aged mice, and 2) a change in the homing pattern of transferred immunocompetent cells to lymphoid tissues in the aged environment.
Coexistence of defective and normal immunologic functions in lymphocytes and macrophages from osteopetrotic (op) rats.
Authors: Hochman N , Wahl L M , Sandberg A L
Published: December 2022

The restoration of normal bone remodeling in osteopetrotic animals by transplantation of spleen or bone marrow cells from normal littermates has suggested that the connective tissue abnormalities associated with this disease may be attributed to defective functions of the cells of the immune system. Examination of several immunologic parameters has revealed that both thymocytes and macrophages from osteopetrotic (op) rats express some dysfunctions but retain other activities. Mitogen-induced proliferation of thymocytes from affected rats is significantly lower than that of thymocytes from normal littermates. However, mitogen-activated thymocytes from op rats produce levels of a chemotactic lymphokine that are similar to those produced by the thymocytes from normal animals. Peritoneal exudate macrophages from op rats are defective in that they migrate minimally in response to a chemotactic lymphokine or C5a. These macrophages do, however, produce lymphocyte-activating factor as efficiently as those from the unaffected littermates. The results presented here, which document immunologic defects in the lymphocytes and macrophages from the op rat, indicate that multiple immunoregulatory mechanisms involved in the degradation of connective tissue may contribute to the skeletal malformations that are present in this animal model.
Inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity by ouabain: relationship between cytotoxic function, glycolysis, and intracellular cation homeostasis.
Authors: Ladisch S , Feig S A
Published: December 2022

Ouabain, a specific inhibitor of membrane Na+K+-ATPase, was used to study the relationship between monovalent cation, homeostasis and cytotoxic effector function. 5 X 10(-6) M ouabain completely inhibited monocyte monovalent cation active transport within 30 min but caused only 50% inhibition of monocyte-mediated antibody-dependent cellular cytotoxicity (MMADCC) in a subsequent 20-hr assay. Longer (6-hr) preincubation of monocytes in ouabain was required for nearly complete inhibition of cytotoxic function. The previously reported augmentation of monocyte glycolysis caused by the sensitizing antiserum was decreased by 71% in 5 X 10(-6) M ouabain, identifying monovalent cation transport as the cellular function utilizing a major portion of the ATP generated by this augmentation of glycolysis. The lag in inhibition of MMADCC indicated, however, that a delayed effect of ouabain (e.g., changes in intracellular [K+] and [Na+]), and not the rapid ouabain inhibition of cation transport, caused inhibition of cytotoxic function. Four additional findings support this interpretation: i) a 30-min preincubation in ouabain caused little inhibition of MMADCC in a 4-hr assay; ii) monocytes lost cytotoxic activity when incubated in medium (0.2 mEq/cytotoxic activity when incubated in medium (0.2 mEq/liter) that reduces intracellular [K+]; iii) the rapid recovery of cytotoxic activity after readjustment of extracellular [K+] to 6 mEq/liter was blocked by ouabain; iv) increasing membrane K+ permeability by valinomycin while blocking active transport by ouabain caused 50% inhibition under conditions in which neither agent alone significantly affected MMADCC. Thus, it is suggested that homeostasis of monocyte intracellular [K+] and [Na+], but not monovalent cation active transport per se, is required for cytotoxic function.
A T cell-derived factor stimulating multipotential hemopoietic stem cells: molecular weight and distinction from T cell growth factor and T cell-derived granulocyte-macrophage colony-stimulating factor.
Authors: Schrader J W , Clark-Lewis I
Published: December 2022

The production of multipotential hemopoietic stem cells (CFUs) in cultures of murine bone marrow cells is supported by medium conditioned by concanavalin A-stimulated T cell hybridoma 123 or spleen cells. We present physiochemical evidence that this activity of these conditioned media, which we have operationally termed CFUs-stimulating activity (CFUs-SA), is due to a new T cell-derived lymphokine. CFUs-SA was shown by gel filtration to reside in a distinct fraction corresponding to a mean apparent m.w. of 29,000, and was distinguishable from T cell growth factor, not only by its lower apparent m.w. but also by chromatography using Phenyl-Sepharose. After isoelectric focusing of neuraminidase-treated conditioned medium, CFUs-SA was found between isoelectric points 5 and 8. In this respect, CFUs-SA appeared similar to another factor, P cell-stimulating factor, which stimulates the growth of persisting (P) cells (homogeneous populations of cells resembling mast cells) and that occurred together with CFUs-SA in both the spleen and hybridoma-conditioned media. Isoelectric focusing separated CFUs-SA from granulocyte-macrophage colony-stimulating factor, which focused as a single peak with an isoelectric point around 5.0. Thus CFUs-SA is due to a T cell-derived factor that is separable from T cell growth factor and T cell-derived granulocyte-macrophage colony-stimulating factor, but has similar properties to P cell-stimulating factor.
Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines: process of selection of lines and characterization of the cells.
Authors: Ben-Nun A , Cohen I R
Published: December 2022

This paper describes alternative ways of deriving lines of rat lymphocytes capable of mediating EAE. The cells were demonstrated to bear markers specific for T lymphocytes and to be negative for surface Ig, and for Fc and complement receptors. The line cells were found to proliferate in vitro specifically in response to myelin basic protein (BP) associated with accessory cells syngeneic at the major histocompatibility complex (MHC). This accessory cell function could not be provided by purified populations of adherent cells from spleen, peritoneal exudates, or bone marrow cultures alone.
Immune complex induced generation of oxygen metabolites by human neutrophils.
Authors: Weiss S J , Ward P A
Published: December 2022

Human neutrophils have been studied for their ability to respond with production of O(2) and H2O2 by human neutrophils contain a 1:2 weight ratio of antigen and antibody (molar ratio of 1.5:1). The metabolic stimulation of leukocytes is a linear function of the total amount of complex used. Complexes containing F(ab')2 are ineffective in stimulating leukocytes to produce O(2) and H2O2. The complexes that maximally stimulate production of O(2) by neutrophils differ from those complexes that are 1) most effective in complement fixation, 2) maximally taken up by neutrophils, and 3) most effective in the induction of enzyme release. These findings suggest that immune complex-induced damage in tissues may reflect the effects of a heterogeneous population of immune complexes.
Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). I. H-2 restriction of the murine humoral immune response to the a and d determinants of HBsAg.
Authors: Milich D R , Chisari F V
Published: December 2022

In hepatitis B virus (HBV) infection correlation of disease activity with major histocompatibility complex (MHC) antigens has been suggested. However, no data are available regarding the nature and regulation of the immune response to the surface viral protein (HBsAg). This consideration and the current emphasis on production of an HBV vaccine led us to investigate the humoral immune response to HBsAg in inbred strains of mice to assess genetic factors that may regulate the humoral anti-HBs response. Studies with H-2 congenic and noncongenic inbred strains revealed the T-dependent humoral immune responses to the group-specific a and subtype-specific d determinants of HBsAg are regulated by gene(s) mapping to the murine MHC. The H-2q haplotype conferred high responsiveness, the H-2s,f haplotypes conferred low to nonresponsiveness, and the H-2a,b,d,k haplotypes were intermediate. Studies of H-2 recombinant strains allowed tentative mapping of regulation of the anti-a response and possibly the anti-d response to the K/I-A, I-B region of the MHC. The H-2-restricted regulation of the humoral immune response to HBsAg was circumvented by immunization with 10-fold higher HBsAg doses. These findings demonstrate a clear linkage between the murine MHC and the regulation of the immune response to specific determinants on HBsAg.
Identification and characterization of excretory-secretory products of Brugia malayi, adult filarial parasites.
Authors: Kaushal N A , Hussain R , Nash T E , Ottesen E A
Published: December 2022

Although E-S antigens may be particularly important for both the pathogenesis and immunodiagnosis of helminth infections, little is known about the immunochemistry or functional roles in human filarial infections. In the present paper, we have done some initial identification and characterization of E-S products of adult Brugia malayi by employing a combination of sensitive biochemical and immunochemical techniques. E-S products, collected by incubating B. malayi adults in vitro in a defined protein-free medium, were radiolabeled with 125I. SDS-polyacrylamide gel electrophoresis (PAGE) and autoradiography of labeled E-S products revealed 11 protein bands in the m.w. range of 10,000 to 70,000. Comparison of radiolabeled E-S products and adult somatic antigen (B.m.A) in SDS-PAGE indicated many common bands, and crossed immunoelectrophoresis and competitive Staph-A RIA confirmed the presence of most E-S antigens in B.m.A. Of the 11 E-S bands, two appeared to be derived from the surface of the adult worms and microfilariae as shown by SDS-PAGE and autoradiography of lodogen surface-labeled parasites; the presence of two host proteins in E-S was detected by crossed-line immunoelectrophoresis. The E-S antigens were highly immunogenic when tested both with rabbit antiserum raised against B.m.A and with a serum pool of patients with natural filarial infection.
Augmentation of delayed-type hypersensitivity to serum proteins by vesicular stomatitis virus infection in mice: virus-suppressor cell interactions.
Authors: Katsura Y , Takaoki Y , Minato N
Published: December 2022

The effects of infection with vesicular stomatitis virus (VSV) on delayed-type hypersensitivity (DTH) to heterologous serum proteins were investigated in mice. DTH was induced by a subcutaneous injection of antigen in complete Freund's adjuvant. Infection with VSV at the time of immunization did not affect the level of DTH elicited 3 wk later. Marked augmentation of DTH was observed only when previously immunized mice were infected with VSV simultaneously with restimulation by soluble antigen; either soluble antigen or the virus infection alone was ineffective. The augmentation was specific to the antigen used for the restimulation; in the mouse previously immunized with both bovine serum albumin (BSA) and human alpha-globulin (HGG), DTH to BSA but not to HGG was augmented by injecting soluble BSA and VSV, and vice versa. These results strongly suggest that cells involved in the suppression of DTH manifestation became susceptible to the virus after specific antigenic restimulation and were then eliminated.
Protection of neonatal mice against herpes simplex virus infection: probable in vivo antibody-dependent cellular cytotoxicity.
Authors: Kohl S , Loo L S
Published: December 2022

Infant mice are extremely susceptible to fatal Herpes simplex virus (HSV) infection. They are unable to produce antibody to HSV, and their leukocytes cannot mediate antibody-dependent cellular cytotoxicity (ADCC) to HSV-infected cells. In order to avoid H-2-dependent effector mechanisms and instead analyze possible in vivo ADCC, a murine model employing adoptive transfer of antibody and human leukocytes was developed. Administration of either human immune globulin or leukocytes i.p. from HSV immune or nonimmune humans could not protect infant C57BL/6 mice from fatal HSV infection. In contrast, a combination of a subneutralizing dilution of globulin and leukocytes from nonimmune or immune human donors, given one day before inoculation, was highly protective against lethal HSV infection. The cells involved included lymphocytes or monocyte-macrophages. At least 5 X 10(6) viable leukocytes (or 1 X 10(6) monocyte-macrophages) and immune serum globulin concentrations as low as 10(-8) were protective. Infected cell monolayer adsorption and DEAE column fractionation demonstrated that the protection by globulin was due to specific antiviral IgG antibody. Protection was n ot seen in animals receiving virus before immune transfer. Protection did not involve synergistic viral neutralization by antibody and cells, as shown by in vitro experiments. Animals receiving globulin and cells, unlike normal infant mice, had circulating antiviral antibody and peritoneal leukocytes able to mediate ADCC to HSV-infected cells. This is the first in vivo evidence for the role of human ADCC. This model also allows for the in vivo evaluation of the ability of cells from immunocompromised humans to curb viral infection.
Repeated isolation of unique Qa2+ Ia+ clonally derived cell lines from Qa2- mice.
Authors: Rosenson R S , Flaherty L , Levine H , Reinisch C L
Published: December 2022

Qa2+ tumor cell lines were previously isolated from individual BALB/cBy (Qa2-) splenic lymphomas induced by murine sarcoma virus-murine leukemia virus-Moloney (MSV-MuLV-M). Two clonally derived cell lines, ORA I-a and Thorbly, and one noncloned cell line, BOMS, expressed Qa2, but neither Ly-1 nor Ly-2 were detected. In order to determine whether eight cloned and two noncloned tumor cell lines all represented a unique population of transformed cells, the presence of a series of surface differentiation antigens as studied. In addition to Qa2, each cell line examined expressed IAd, IEd, H-2Kd, H-2Dd, and receptors for C3b and the Fc portion of immunoglobulin (Ig). Neither Thy-1.2 nor Ig were detected on the cell surfaces, and cytoplasmic Ig was not precipitated from metabolically radiolabeled and detergent-solubilized cell extracts. However, monocyte specific alpha-napththyl acetate esterase-containing granules were present in all cell lines examined. Therefore, a unique Qa2+ monocytic cell is repeatedly isolated after chronic MSV-MuLV-M infection. Further analysis of these cells may provide insight into both the regulation of Qa2 expression and the interactions between monocytes and lymphocytes during leukemogenesis.