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H Jyonouchi

Publications and source records attributed to H Jyonouchi.

At least 55 records · Page 3Linked to original sources
PubMed1991

Soluble Fc epsilon R II levels in normal children and patients with immunodeficiency diseases.

CD23 is expressed on mature B cells and is identical to a low-affinity IgE Fc epsilon receptor type II (Fc epsilon R II). The C terminal portion of CD23 is released to the serum as soluble Fc epsilon R II (sFc epsilon R II), which may be involved in regulation of IgE synthesis. We studied sFc epsilon R II levels in normal children and in patients with immunodeficiencies, including common variable immunodeficiency (CVI), partial DiGeorge syndrome, and immunodeficiency associated with ectodermal dysplasia to examine the relationship of sFc epsilon R II levels to B cell numbers and other immunoparameters. Serum Fc epsilon R II levels are higher in younger children (younger than 3 years) and decline gradually with age. In 11 patients with CVI with normal numbers of B cells (greater than 6%), sFc epsilon R II levels were comparable to that of control subjects. Five patients with CVI with deficiencies of peripheral B cells had levels of sFc epsilon R II similar to levels of control subjects. In all but one patient with partial DiGeorge syndrome, sFc epsilon R II levels were not significantly elevated, despite the presence of elevated peripheral B cell numbers. Of six patients with ectodermal dysplasia, four demonstrated increased Fc epsilon R II levels, a finding not correlated with serum IgE levels or with peripheral eosinophil or B cell numbers.

Adolescent↗
PubMed1991

Studies of immunomodulating actions of carotenoids. I. Effects of beta-carotene and astaxanthin on murine lymphocyte functions and cell surface marker expression in in vitro culture system.

The immunomodulating effects of carotenoids (beta-carotene and astaxanthin) on mouse lymphocytes were studied in in vitro culture system by use of assay for mitogen responses of spleen cells, thymocyte proliferation, interleukin 2 production, and antibody (Ab) production in vitro in response to sheep red blood cells. Changes of cell surface markers on spleen lymphocytes including Ia antigen (Ag), surface immunoglobulin, B220, and Thy-1 Ag were also examined. At a concentration of 10(-8) M, carotenoids did not show any significant effect on mitogen responses (phytohemagglutinin P and concanavalin A) on murine spleen cells, irrespective of the concentrations of mitogens used. Interleukin 2 production by murine spleen cells was not significantly altered by carotenoids in the culture media (10(-7) to 10(-9) M). [3H]thymidine incorporation by B6 thymocytes was somewhat enhanced in the presence of astaxanthin or beta-carotene when cultured in the concentration of 10(6)/ml. At higher concentrations of cells (5 x 10(6)/ml), such an effect was not observed. In assays of in vitro Ab production in response to sheep red blood cells, B6 spleen cells produced significantly more Ab-forming cells (plaque-forming cells, immunoglobulins M and G) in the presence of astaxanthin (greater than 10(-8) M) but not beta-carotene. Expression of Ia Ag seemed to be moderately enhanced on both Thy-1+ and Thy-1- spleen cells in the presence of astaxanthin (greater than 10(-9) M) but not beta-carotene. The expression of Thy-1 and surface immunoglobulin seemed unchanged with the treatment of these carotenoids. These results indicate that immunomodulating actions of carotenoids are not necessarily related to provitamin A activity, because astaxanthin, which does not have provitamin A activity, showed more significant effects in these bioassays and also indicate that such actions of carotenoid demonstrated in this study may be difficult to explain only by its oxygen-quenching capacity.

Adjuvants, Immunologic↗
PubMed1991

Zinc depletion modifies CD5 expression by 70Z/3 murine pre-B leukemia cell line.

CD5 expression on B cells is regulated by certain humoral factors. In a pre-B leukemia cell line 70Z/3, we found that interleukin 4 down-regulates it. Herein, we report that zinc influences spontaneous CD5 expression by this cell line as well as actions of these factors on CD5 expression considerably. In zinc-depleted culture media, spontaneous CD5 expression by 70Z/3 cells was enhanced. In contrast, the down-regulatory action of interleukin 4 was significantly reduced under culture conditions of zinc depletion. The supplementation of zinc to physiologic concentrations (1 to 2 microM) abolished such effects of zinc-depleted medium. The reduction of the suppressive action of interleukin 4 was observed at the level of gene expression. However, CD5 mRNA expression enhanced by lipopolysaccharide or NZB-SF was not further enhanced under conditions of zinc deficiency. These observations may suggest that CD5 expression by malignant or even normal B cells may be influenced by cellular/serum zinc levels.

Animals↗
PubMed1990

Up-regulation and down-regulation of cell surface and mRNA expression of CD5 antigen by various humoral factors on murine 70Z/3 pre-B cell leukemia cell line: IL-4 down-regulates CD5 antigen expression.

CD5, a pan-T cell antigen, is expressed on a minor subset of normal B lymphocytes and on cells of most B lineage tumors or transformed B cells in both man and animal models. In the present study, the effects of various humoral factors on CD5 expression by cells of a subcloned 70Z/3 murine pre-B leukemia cell line were investigated. Among the humoral factors studied, only LPS up-regulated CD5 expression on 70Z/3 cells (three- to fourfold) in a dose-dependent manner. However, this up-regulatory effect of LPS was not observed when cells were cultured in serum-free medium. NZB-serum factor (NZB-SF), a cytokine we have identified and shown to enhance the maturation and proliferation of immature B cells, synergistically enhanced CD5 expression in the presence of suboptimal doses of LPS. IL-4 down-regulated CD5 expression by 70Z/3 cells induced by LPS or LPS plus NZB-SF in a dose-dependent manner. IL-4 also suppressed spontaneous CD5 expression by 70Z/3 cells. No other cytokine tested showed an inhibitory effect. LPS, IFN-gamma, NZB-SF, and IL-1 enhanced sIg expression on 70Z/3 cells and their action on sIg expression was not inhibited by IL-4. Thus, the down-regulatory action of IL-4 on CD5 expression appeared specific for this antigen. IFN-gamma, which inhibits IL-4 induced CD23 and DR expression on B cells, does not abolish the down-regulatory action of IL-4 on CD5 expression by 70Z/3 cells. Changes in mRNA levels on coding CD5 were also examined following the incubation of 70Z/3 cells (24 hr) in the presence of humoral factors which can influence CD5 Ag expression. The levels of mRNA for CD5 Ag were moderately increased in the presence of LPS and NZB-SF. IL-4 appeared to suppress the actions of NZB-SF and LPS at least in part by reducing the levels of mRNA encoding CD5.

Animals↗
PubMed1988

The presence of autoantibodies specific for NZB serum factors in adult NZB mice and the establishment of monoclonal autoantibodies against these humoral factors.

Humoral factors in serum of young NZB mice enhance maturation of B-lymphocyte precursors in vitro. A blot ELISA assay identified autoantibodies against the serum factors. NZB-SFs (designated NZB-SF alpha, pI 3.5-4.0, and NZB-SF beta, pI 7.8) were purified by sequential steps. Both had a molecular weight (MW) of approximately 23,000 in SDS-PAGE. NZB mice develop autoantibodies against NZB-SFs by 2 months of age; titers increased progressively with age. Non-autoimmune-prone mice did not produce autoantibodies against NZB-SFs. We then developed two hybridoma clones, IIC1C1 and IIC1M4, which produce monoclonal autoantibodies against NZB-SF alpha and NZB-SF beta, respectively. Both IgM autoantibodies could be affinity purified with a column of CNBr-Sepharose 4B gel conjugated with anti-mouse IgM antibody. Neither IIC1C1 nor IIC1M4 abolished bioactivity of recombinant mouse IL-1 alpha, human IL-1, mouse, rat, or human IL-2, mouse IL-3, or colony-stimulating factor. Neither antibody reacted to recombinant mouse IL-1 alpha, IL-4, TNF alpha, or IFN gamma in blot ELISA assays. Monoclonal autoantibodies IIC1C1 and IIC1M4 were used to purify NZB-SFs. SDS-PAGE of the affinity-purified NZB-SFs revealed bands of 23 and 60 kDa, and proteins extracted from the bands were reactive to our monoclonal autoantibodies.

Animals↗
PubMed1987

IL 1-like activities present in murine amniotic fluid. A significantly larger amount of IL 1 beta-like activity is present in the amniotic fluid of autoimmune NZB mice.

Rapid progress in studies of cytokines have clarified their roles in processes of lymphocyte proliferation and differentiation. However, the involvement of these molecules in lymphopoiesis during embryonic development has not yet been well documented. In this study we screened for possible existence of cytokines that influence lymphopoiesis in murine amniotic fluid (AF) obtained from non-autoimmune prone "normal" strains of mice (CBA/J, BALB/c, A/J, SWR, and C57B/6) and autoimmune-prone NZB mice. Significant colony stimulating activity-1 (CSA-1)-like activities were found in AF of all of the strains tested, but relatively low activities were present in AF of NZB mice. No interleukin 2 (IL 2) or interleukin 3 (IL 3)-like activities were detected, Weak IL 1-like activity was found in AF of most of the strains tested; however, the results of the standard thymocyte proliferation assays varied with each AF sample. This variation is probably related to the presence of nonspecific inhibitors including alpha-fetoprotein in murine AF. Therefore, pooled AF from CBA and NZB strains of mice were subjected to several purification procedures to assess the actual amount of IL 1-like activity present in murine AF. After (NH4)2SO4 precipitation and hydrophobic phenyl-Sepharose chromatography, the measurable level of IL 1-like activity could be increased significantly. With lentil-lectin affinity chromatography, IL 1-like activity was completely dissociated from CSA-like activity. Moreover, a significantly larger amount of IL 1-like activity was found in NZB AF fractions (approximately sixfold higher). Apparent pI values estimated by preparative isoelectric focusing (IEF) were 5.9, 7.2, and 7.4 in CBA AF fractions, and 6.5 and 7.3 in NZB AF fractions. The NZB AF fraction with pI of 7.3 showed significantly higher IL 1 activity than the other fractions studied. These partially purified molecules were found to be resistant to pH 2 and the reducing agent, 2-mercaptoethanol, but were inactivated by heat (56 degrees C, 1 hr) or trypsin. None of the fractions showed IL 2-like activity but some that had IL 1-like activity induced IL 2 production in a IL 1-dependent, IL 2-producing B lymphoma cell line. Apparent m.w. of these IL 1-like activities were 14,000, 14,500, 17,000, 18,000, and 21,000 in CBA AF fractions, and 15,000, 19,000, and 21,000 in NZB AF fractions according to SDS-polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1985

Age-dependent changes in B lymphocyte lineage cell populations of autoimmune-prone BXSB mice.

BXSB mice, a recently developed autoimmune strain, develop a human lupus-like disease with B cell hyperplasia in peripheral lymphoid organs. Unlike other experimental models of autoimmunity and human lupus, BXSB male mice manifest accelerated autoimmune phenomena through the influence of a Y chromosome-linked enhancing factor. The present studies were performed to investigate the features of B lymphopoiesis in BXSB mice and to determine whether differences exist between BXSB males and females in this respect. B lineage cell populations in the marrow of BXSB mice were identified phenotypically by studying the cytoplasmic mu-heavy chains of IgM (c mu), and functionally by their ability to acquire clonability and sIg in short-term liquid cultures. Male BXSB mice became deficient in both the precursors of functional B cells and c mu + pre-B cells by the age of 8 to 12 wk. This followed a transient increase in this population, which peaked when the mice were 2 to 4 wk old. In females, substantial numbers of functional B cell precursors and c mu + cells were maintained until more than 4 mo of age. Cells lacking Ig but bearing a B lineage cell antigen (14.8) were elevated in numbers in both BXSB males and females until 16 wk of age when compared to normal strains of mice. At the time pre-B cells and functional B precursors were elevated in numbers, some sIg- cells were shown to form colonies in mitogen-stimulated semisolid agar cultures without a period of preculture. Most of these sIg- cells seemed to bear the B lineage cell antigen (14.8). They were independent of both G-10 adherent regulatory cells and Thy-1+ cells for their colony formation. These results indicate that B lymphocyte formation may be maintained in a hyperactive state in BXSB females, whereas males become deficient in B cell precursors very early in life. This early decline might be related to the accelerated development of autoimmune disease in BXSB mice. Bone marrow transplantation studies showed that these unusual characteristics of B lymphopoiesis were reciprocally transferable with unseparated bone marrow cells between BXSB males and females. This finding indicates that sex hormones are not a critical variable in abnormal B lymphocyte formation in this strain, and that the premature deficiency of immediate B precursors in males may be regulated by a genetic factor(s) located on the Y chromosome.

Aging↗
PubMed1985

Humoral factors in very young NZB mice that enhance the maturation of normal B cell precursors. Partial purification and characterization.

Soluble factors that enhance maturation of murine B lineage precursor cells in vitro were partially purified from the serum of very young NZB mice and characterized biochemically and biologically. Activity was initially detected by induction of colony-forming activity and surface immunoglobulin (sIg) on normal sIg- marrow cells as well as responsiveness of a pre-B cell line. Pooled sera from 4- to 5-wk-old NZB mice were initially fractionated on Sephacryl S-300 and Sephadex G-100 superfine columns. Fractions with activity (corresponding to m.w. of 15,000 to 45,000) were pooled and further separated. The activity was eluted as a single peak by hydrophobic (phenyl-Sepharose, with 0.8 M (NH4)2SO4) and lentil lectin affinity chromatography but resolved into three distinct peaks in preparative isoelectric focusing (IEF), with pI values of 3.5, 7.8, and 8.4. The latter two merged into a single peak with a pI value of 8.8 when the sample was further treated with neuraminidase before IEF. These three IEF fractions, each of which were enriched at least 1000-fold in specific activity relative to starting serum, were then characterized. Each was stable at pH 2 but sensitive to trypsin, 10 M urea, and heat treatment (56 degrees C for 1 hr). In nonreduced SDS-poly-acrylamide gel electrophoresis, their mobilities corresponded to m.w. of 17,000 for peak I (pI 3.5), 15,000 for peak II (pI 7.8), and 15,000 for peak III (pI 8.4). Interleukin 1, interleukin 2, interleukin 3, colony-stimulating factor for granulocyte and macrophage progenitors, antiviral, or B cell growth factor type I-like activities were not demonstrable. Peaks II and III, but not peak I, induced Ig secretion of anti-stimulated B cells. Peak I was also less effective than peaks II and III in induction of sIg on an established pre-B cell line. However, all fractions were equally effective in enhancing maturation of normal sIg- B lineage cells. Thus, serum from 4- to 5-wk-old NZB mice contains at least two distinct soluble factors that can enhance the maturation of sIg- B lineage cells in vitro. The biologic and biochemical characteristics of these factors appear to differ from those of previously well-defined cytokines.

Animals↗
PubMed1984

Precocious and enhanced functional maturation of B lineage cells in New Zealand Black mice during embryonic development.

Previous reports suggest that large numbers of immunoglobulin-secreting cells appear in tissues of NZB strain mice from the time of birth. In this study, we investigated the development of B lineage cells during embryonic life and found that they were present 2-3 d earlier and in higher numbers in NZB embryos than several other strains of mice. That is, liver cell suspensions from NZB embryos contained larger numbers of surface Ig (sIg)- cells that could form B cell colonies in mitogen-dependent semisolid agar culture. Sephadex G-10-adherent cell depletion diminished numbers of colonies and this was partially restored by addition of humoral factors. The latter were partially purified from serum of very young NZB mice. These findings document that abnormal changes take place in B lineage cells and possibly also in cells that regulate their maturation in NZB strain mice at a very early stage of development.

Aging↗
PubMed1984

Analysis of the effects of erythrocytes on mitogen-dependent clonal proliferation of murine B lymphocytes.

Addition of intact erythrocytes to semisolid agar cultures of murine B cells dramatically improves cloning efficiency and affects colony morphology. In this study, we investigated possible mechanisms through which this might occur. Specific modification of sheep erythrocyte (SRBC) membranes by treatment with trypsin but not other enzymes improved colony potentiation and erythrocytes from rats, mice, and humans were also effective after trypsin treatment. In addition, autoantibody-coated murine erythrocytes were superior to normal cells in this regard. These observations suggest that erythrocytes enhance lymphocyte survival and/or proliferation by means of particular membrane-mediated processes. The possible importance of erythrocytes as scavengers of toxic hydroxyl radicals was also investigated. Deliberately generated radicals formed by addition of dihydroxyfumaric acid and iron were effectively countered by addition of SRBC. More detailed analyses revealed that of several endogenously produced toxic species, hydrogen peroxide may be the most important under ordinary culture conditions. That is, addition of catalase but not superoxide dismutase or mannitol improved cloning efficiency in cultures lacking SRBC. These studies suggest that erythrocytes have a beneficial effect on lymphocyte survival and function in culture through at least two mechanisms.

Animals↗
PubMed1983

Changes in B lineage cell population in liver and spleen of normal neonatal mice.

The frequency and characteristics of B lymphocyte lineage cells in neonatal murine liver and spleen were studied during the first 10 days after birth. These were distinguished as B cells with surface IgM (slgM), immediate precursors of B cells (pre-B cells) lacking slgM but containing micron-heavy chains of IgM, and earlier precursors that did not synthesize immunoglobulin but could be detected with monoclonal 14.8 antibody. Experiments were also done to relate these to cells capable of clonal proliferation in mitogen-containing semisolid agar cultures and cells that acquire this function only after preculture in liquid medium. Newborn liver contained large numbers of early precursors as well as pre-B cells, and culture studies revealed that a majority of the colony-forming B cells present at that time were slg-. Adherent accessory cells in newborn liver suspensions facilitated the maturation of these into functional B cells in vitro. At most ages, however, numbers of slg+ B cells detected in that tissue were surprisingly low. Possible explanations for this include a rapid exit of newly formed B cells and their immediate precursors from liver and/or a high rate of abortive lg gene rearrangements during the neonatal period. In contrast, whereas the spleen contained early precursors and pre-B cells at birth, these cells steadily declined in number with age as the numbers of slgM+ B cells increased. Adherent cells in liver but not spleen of immunodeficient CBA/N mice suppressed B lymphocyte formation in semisolid or liquid cultures. These observations document population dynamics in B lineage cells during a critical period of development.

Animals↗
PubMed1983

B lymphocyte lineage cells in newborn and very young NZB mice: evidence for regulatory disorders affecting B cell formation.

As adults, NZB mice have a severe deficiency of identifiable precursors of B lymphocytes, but this is preceded by a time when B cells and their immediate precursors are present in bone marrow in elevated numbers. Our present studies indicate that the final stages of B cell formation may be proceeding at a greater than normal rate at 4 wk of age. At this time, large numbers of sIg- B cell precursors can be identified in NZB but not in normal CBA/H or DBA/2 marrow that can respond to mitogens in semisolid agar cultures without preculture. Colony formation by these precursors was dependent on the presence of Sephadex G-10-adherent cells in the suspensions. In this respect, 4-wk-old NZB marrow was similar to spleen and liver of normal CBA/H newborn mice. Mixing experiments suggested that hyperactive regulatory cells present in young NZB marrow may promote functional maturation of normal pre-B cells from CBA/H or DBA/2 mice. In addition, potent substances present in the serum of young but not older NZB mice produced the same effect. Factor-mediated enhancement of clonal proliferation by sIg- precursors was not dependent on adherent cells and required more than brief exposure of the cells to young NZB serum. These are all indications that abnormalities of B lineage differentiation in young NZB marrow may be attributable to microenvironmental elements. Congeneic, B cell-deficient NZB.xid mice, however, lacked hyperactive regulatory cell function and serum factors that characterize NZB mice of this age. A study was also made of B cell precursors in newborn spleen and liver of NZB mice, and abnormal shifts of populations of B lineage cells were already present by that time. These observations support previous contentions that humoral immunity is precocious and abnormally regulated in NZB mice.

Aging↗
PubMed1982

Age-dependent deficiency of B lymphocyte lineage precursors in NZB mice.

Adult NZB mice (greater than 15 wk old) have very few bone marrow cells that can give rise to sIg+ clonable B cells during liquid culture. This deficiency corresponds to extremely low numbers of cells with cytoplasmic but not surface mu chains of IgM and reduced numbers of cells bearing a high molecular weight B-lineage antigen. Depletion of Thy-1-bearing cells and appropriate mixing experiments did not provide evidence either that suppressor cells are responsible for this phenomenon or that accessory cells are defective in NZB mice. Nor did it seem that B cells were being produced in extramedullary sites. B cell precursors were detectable in very young NZB mice, exceeded control values at 4-5 wk of age, and then declined rapidly. In contrast, these persisted for greater than 1 yr in normal BALB/c, DBA/2, and CBA/H mice. It appears possible that intermediate stages in B-lineage differentiation become prematurely exhausted through an accelerated aging process in NZB mice. These chronological changes have implications for understanding the sequence of events that lead to B lymphocyte formation and the processes that normally regulate it.

Aging↗
PubMed1981

Reciprocal transfer of abnormalities in clonable B lymphocytes and myeloid progenitors between NZB and DBA/2 mice.

Previous studies in this laboratory revealed that NZB mice have abnormalities of myeloid progenitor populations from an early age such that they are poorly responsive to a particular type of colony-stimulating activity (CSA). In addition, these mice develop abnormally high numbers of B cells that can be cloned in semisolid agar cultures and that are atypical in resisting inhibition by anti-mu antibodies. To investigate whether these abnormalities, like other autoimmune phenomena studied previously, are transferrable with hemopoietic cell grafts, we performed reciprocal bone marrow transplants between NZB and normal DBA/2 mice. Irradiated control mice given syngeneic marrow did not change with respect to any of the parameters that were measured. In contrast, DBA/2 recipients of NZB marrow were indistinguishable from NZB mice in terms of CSA responses and incidences of anti-mu resistant B cells. The proportions but not total numbers of clonable B cells ere elevated in these mice until at least 16 wk after grafting. Conversely, NZB mice given DBA/2 cells had all of the normal characteristics of DBA/2 mice. Transplantation did not cause significant changes in hematocrits, reticulocyte counts, or spleen weights. Therefore, all elements necessary for expression of these lymphoid and nonlymphoid abnormalities of NZB mice are intrinsic to radiosensitive hemopoietic cells.

Animals↗