scholarly journals ONTOGENY OF B-LYMPHOCYTE FUNCTION

1974 ◽  
Vol 140 (5) ◽  
pp. 1285-1302 ◽  
Author(s):  
Edmond A. Goidl ◽  
Gregory W. Siskind
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Fetal Liver ◽  
Lymphoid Tissues ◽  
Lymphocyte Function ◽  
A Cell ◽  
Neonatal Liver ◽  
Thymus Cells

The ontogeny of the ability of B lymphocytes to produce an antihapten response which is heterogeneous with respect to affinity for the antigenic determinant was studied in a cell transfer system. The heterogeneity of affinity of the immune response of lethally irradiated mice reconstituted with syngeneic, adult thymus cells and fetal or neonatal tissues as a source of B lymphocytes was studied. It was found that B cells from 17 day fetal liver or neonatal liver are highly restricted with respect to heterogeneity of affinity as compared with adult spleen or bone marrow. The B-cell population achieves an adult character with respect to heterogeneity of affinity by 2 wk of age. The peripheral lymphoid tissues (spleen) appear to mature in this respect more rapidly than do central lymphoid tissues (bone marrow). Spleens from 10-day old donors behave in an adult, heterogeneous manner while bone marrow from the same donors exhibit a marked restriction in heterogeneity of affinity. Germfree mice produce an immune response which is indistinguishable from conventionally reared adult animals with respect to heterogeneity of affinity. The earlier appearance of the ability to transfer a heterogeneous immune response in spleen as compared with bone marrow suggests that the increasing heterogeneity of the B-lymphocyte population which occurs between birth and 2 wk of age is the result of a differentiation event and not of a somatic mutation or recombination event.

scholarly journals Ontogeny of B-lymphocyte function. V. Thymus cell involvement in the functional maturation of B-lymphocytes from fetal mice transferred into adult irradiated hosts.

1978 ◽  
Vol 147 (1) ◽  
pp. 196-206 ◽  
Author(s):  
D H Sherr ◽  
M R Szewczuk ◽  
G W Siskind
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Fetal Liver ◽  
Lymphocyte Function ◽  
Thymus Cell ◽  
Functional Maturation ◽  
Fetal Mice ◽  
Thymus Cells ◽  
Adult Thymus

Lethally irradiated mice reconstituted with adult thymus cells and neonatal or fetal liver cells produce an anti-2,4-dinitrophenyl or anti-bovine gamma globulin response of restricted heterogeneity of affinity in comparison with the response of mice reconstituted with B cells from adult donors. In addition, mice reconstituted with day 15 fetal B cells and adult thymus cells produce relatively few indirect plaque-forming cells (PFC). It was found that B cells acquire the capacity to produce a heterogeneous response, of predominantly indirect PFC within 7 days of transfer only when thymus cells are transferred along with the B cells. B cells from fetal or neonatal donors transferred without young adult thymus cells develop the capacity to generate indirect PFC within 13 days after transfer to adult recipients, but continue to produce a response of restricted heterogeneity of affinity for up to 28 days after transfer. Thus, it has been shown that cells present in the thymus facilitate, or are necessary for the functional maturation of B lymphocytes. Furthermore, the data suggest that maturation of the B-cell population to produce a heterogeneous response is controlled independently of its maturation to be capable of producing indirect PFC.

scholarly journals Ontogeny of B-lymphocyte function. II. Ability of endotoxin to increase the heterogeneity of affinity of the immune response of B lymphocytes from fetal mice.

1976 ◽  
Vol 143 (6) ◽  
pp. 1503-1520 ◽  
Author(s):  
E A Goidl ◽  
J Klass ◽  
G W Siskind
Keyword(s):  
B Lymphocytes ◽  
B Lymphocyte ◽  
Fetal Liver ◽  
Cell Activity ◽  
Primary Response ◽  
Secondary Response ◽  
Fetal Life ◽  
Lymphocyte Function ◽  
Adult Type ◽  
High Affinity

The ontogeny of the functional capacity of B lymphocytes to generate a heterogeneous response to a haptenic determinant was studied by cell transfer techniques in LAF1 mice. Fetal liver, as a source of B lymphocytes, was transferred into adult, syngeneic, irradiated animals. All recipients received excess adult thymus cells so that T-cell activity did not limit the response and were immunized with DNP-BGG. The heterogeneity of avidity of their anti-DNP PFC response was assayed by hapten inhibition of plaque formation. Animals reconstituted with B lymphocytes from fetal donors produced a response that is highly restricted with respect to heterogeneity of affinity. Transfer studies using multiple fetal donors or mixtures of adult and neonatal cells for reconstitution suggest that the restriction in heterogeneity is not the consequence of suppressor T-lymphocyte activity. With animals reconstituted with B cells from day 16 or older fetal donors, injection of LPS together with antigen converted the response to a heterogeneous "adult-type" response. With animals reconstituted with B lymphocytes from day 14 fetal liver DxSO4, but not LPS, could convert the response to a highly heterogeneous one. Animals reconstituted with day 14 or 16 fetal liver as source of B lymphocytes were capable of producing a heterogeneous secondary response despite the fact that their primary response was of restricted heterogeneity. This implies the selection of high affinity B-memory cells, in the absence of high affinity PFC during the primary response with fetal B lymphocytes. Animals reconstituted with day 14 or 16 fetal liver produce only direct PFC, while animals reconstituted with day 18 fetal liver produce both direct and indirect PFC. Three differentiation events have therefore been defined in the functional development of B lymphocytes: (a) between day 14 and day 16 of fetal life they acquire responsiveness to LPS; (B) BETWEEN DAY 16 AND 18 OF FETAL DEVELOPMENT THEY ACQUire the capacity to produce indirect PFC; (C) between day 7 and 10 after birth they acquire the capacity to give a heterogeneous response after normal immunization. In addition, it was shown that LAF1 mice already have all of the information required to produce an "adult-type" heterogeneous anti-DNP response at day 14 of fetal life.

Ontogeny of B lymphocyte function VIII. Failure of thymus cells from aged donors to induce the functional maturation of B lymphocytes from immature donors

1980 ◽  
Vol 10 (12) ◽  
pp. 918-923 ◽  
Author(s):  
Myron R. Szewczuk ◽  
Rosemarie H. Dekruyff ◽  
Edmond A. Goidl ◽  
Marc E. Weksler ◽  
Gregory W. Siskind
Keyword(s):  
B Lymphocytes ◽  
B Lymphocyte ◽  
Lymphocyte Function ◽  
Functional Maturation ◽  
Thymus Cells

Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro

1992 ◽  
Vol 12 (2) ◽  
pp. 518-530
Author(s):  
R Palacios ◽  
J Samaridis
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Stromal Cells ◽  
B Lymphocyte ◽  
Germ Line ◽  
Fetal Liver ◽  
Rag 1 ◽  
B Cell Precursors

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.

scholarly journals DISTINCT EVENTS IN THE IMMUNE RESPONSE ELICITED BY TRANSFERRED MARROW AND THYMUS CELLS

1969 ◽  
Vol 130 (6) ◽  
pp. 1243-1261 ◽  
Author(s):  
G. M. Shearer ◽  
G. Cudkowicz
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Bone Marrow Cells ◽  
Second Step ◽  
Cell Divisions ◽  
Cellular Events ◽  
Antigen Complex ◽  
Fresh Bone ◽  
Thymus Cells ◽  
Marrow Cells

Marrow cells and thymocytes of unprimed donor mice were transplanted separately into X-irradiated syngeneic hosts, with or without sheep erythrocytes (SRBC). Antigen-dependent changes in number or function of potentially immunocompetent cells were assessed by retransplantation of thymus-derived cells with fresh bone marrow cells and SRBC; of marrow-derived cells with fresh thymocytes and SRBC; and of thymus-derived with marrow-derived cells and SRBC. Plaque-forming cells (PFC) of the direct (IgM) and indirect (IgG) classes were enumerated in spleens of secondary host mice at the time of peak responses. By using this two-step design, it was shown (a) that thymus, but not bone marrow, contained antigen-reactive cells (ARC) capable of initiating the immune response to SRBC (first step), and (b) that the same antigen complex that activated thymic ARC was required for the subsequent interaction between thymus-derived and marrow cells and/or for PFC production (second step). Thymic ARC separated from marrow cells but exposed to SRBC proliferated and generated specific inducer cells. These were the cells that interacted with marrow precursors of PFC to form the elementary units for plaque responses to SRBC, i.e. the class- and specificity-restricted antigen-sensitive units. It was estimated that each ARC generated 80–800 inducer cells in 4 days by way of a minimum of 6–10 cell divisions. On the basis of the available evidence, a simple model was outlined for cellular events in the immune response to SRBC.

Synergistic Cooperation Between T and B Lymphocytes from Old Mice in the Production of Auto-Anti-Idiotypic Antibody Regulation in Adult Irradiated Hosts

1982 ◽  
Vol 1 (1-2) ◽  
pp. 3-10 ◽  
Author(s):  
Myron R. Szewczuk
Keyword(s):  
B Cells ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Intrinsic Property ◽  
Adoptive Cell Transfer ◽  
Cell Transfer ◽  
Lymphocyte Population ◽  
Thymus Cells ◽  
Old Mice ◽  
Idiotypic Antibody

ABSTRACTThe effect of age on the ability of B lymphocytes and thymus cells from donors of various ages to be capable of producing an anti-idiotype-blocked, hapten-augmentable PFC was studied by adoptive cell transfer techniques. Lethally irradiated mice were reconstituted with syngeneic B lymphocytes and thymus cells from donors of various ages. Recipients were immunized with trinitrophenylated bovine gamma globulin (TNP-BGG) one or seven days after cell transfer. Splenic IgG anti-TNP plaque-forming cell (PFC) responses were assayed in the absence and presence of hapten for anti-idiotype (Id)-blocked, hapten-augmentable PFC, 14 days after immunization. It was found that the B lymphocyte population from 2 month old donors together with thymus cells from donors of various ages (2 to 19 months) were incapable of reconstituting mice to produce anti-Id-blocked, hapten-augmentable PFC. Similar results were obtained when mice were reconstituted with thymus cells from 2-month-old donors together with B cells from donors of various ages (2 to 14 months). In contrast, mice reconstituted with B cells plus thymus cells from the same 8-month or older donors produced a significantly high percentage of anti-Id-block, hapten augmentable PFC. Mice reconstituted with B cells from 8 months or older donors plus thymus cells from donors of various ages (8 to 19) months also produced a significantly high percentage of hapten-augmentable PFC. Experiments with B cells and thymus cells from 2-or 8-month old donors parked in lethally irradiated 2-or 8-months old recipients for 7 days revealed that neither lymphocytes from old donors or old recipients were capable of inducing the appearance of anti-Id-blocked, hapten-augmentable PFC in the lymphocyte population from 2-month-old donors. Thus, the results of this study indicate syner-gistic co-operation between B lymphocytes and thymus cells from old donors for the production of auto-anti-idiotypic antibody regulation with age. This production of auto-anti-Id antibody with age seems not to be an induced maturation event but perhaps an intrinsic property unique to lymphocytes from old donors.

scholarly journals [18F]-Fluorodeoxyglucose Uptake in Lymphoid Tissue Serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Virus Infection

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Julie Dyall ◽  
Reed F. Johnson ◽  
Svetlana Chefer ◽  
Christopher Leyson ◽  
David Thomasson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Lymph Nodes ◽  
Metabolic Activity ◽  
Fdg Pet ◽  
Ct Imaging ◽  
Lymphoid Tissues ◽  
Fdg Uptake ◽  
Pet Ct ◽  
Fdg Pet Ct

ABSTRACT Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.

scholarly journals B lymphocytes express and lose syndecan at specific stages of differentiation.

1989 ◽  
Vol 1 (1) ◽  
pp. 27-35 ◽  
Author(s):  
R D Sanderson ◽  
P Lalor ◽  
M Bernfield
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Expression ◽  
Cell Stage ◽  
Precursor B Cells

Lymphopoietic cells require interactions with bone marrow stroma for normal maturation and show changes in adhesion to matrix during their differentiation. Syndecan, a heparan sulfate-rich integral membrane proteoglycan, functions as a matrix receptor by binding cells to interstitial collagens, fibronectin, and thrombospondin. Therefore, we asked whether syndecan was present on the surface of lymphopoietic cells. In bone marrow, we find syndecan only on precursor B cells. Expression changes with pre-B cell maturation in the marrow and with B-lymphocyte differentiation to plasma cells in interstitial matrices. Syndecan on B cell precursors is more heterogeneous and slightly larger than on plasma cells. Syndecan 1) is lost immediately before maturation and release of B lymphocytes into the circulation, 2) is absent on circulating and peripheral B lymphocytes, and 3) is reexpressed upon their differentiation into immobilized plasma cells. Thus, syndecan is expressed only when and where B lymphocytes associate with extracellular matrix. These results indicate that B cells differentiating in vivo alter their matrix receptor expression and suggest a role for syndecan in B cell stage-specific adhesion.

scholarly journals B-lymphocyte heterogeneity: ontogenetic development and organ distribution of B-lymphocyte populations defined by their density of surface immunoglobulin.

1976 ◽  
Vol 144 (2) ◽  
pp. 494-506 ◽  
Author(s):  
I Scher ◽  
S O Sharrow ◽  
R Wistar ◽  
R Asofsky ◽  
W E Paul
Keyword(s):  
Bone Marrow ◽  
B Lymphocytes ◽  
B Lymphocyte ◽  
Bone Marrow Cells ◽  
Large Population ◽  
Organ Distribution ◽  
Spleen Cells ◽  
Adult Bone Marrow ◽  
Flow Microfluorometry ◽  
Adult Bone

The density of total Ig and of IgM, IgG1, IgG2, and IgA on the surface of adult murine splenic B lymphocytes was measured using the technique of rapid flow microfluorometry. In addition, the density of total surface Ig and of IgM on B lymphocytes derived from adult bone marrow, lymph nodes, and Peyer's patches, and from neonatal spleen was determined. Adult spleen and lymph node B lymphocytes are characterized by the presence of a large population of cells with a low-to-intermediate density of total surface Ig, which is seen as a peak in the fluorescence profiles when these cells are labeled with fluorescein-conjugated (F1) anti-Ig. This peak is not detected when neonatal spleen or adult bone marrow are examined; the development of this peak among spleen cells occurs during the first 4 wk of life. Although the characteristic fluorescence intensity peak is not seen when adult spleen cells are labeled with Fl anti-mu, changes in the density of surface IgM do occur during the first few weeks of life and are detected as a decrease in the frequency of cells which have relatively large amounts of surface IgM. The differences seen in the fluorescence patterns of adult spleen cells labeled with Fl anti-Ig and Fl anti-mu may be due to the appearance of IgD on the surface of mature splenic B lymphocytes. This is supported by the similarity of the fluorescence profiles of adult bone marrow cells stained with Fl anti-Ig and Fl anti-mu, as the latter population of cells is reported to lack surface IgD.

Some aspects of the H-2 system, the major histocompatibility system in the mouse

1978 ◽  
Vol 202 (1146) ◽  
pp. 117-158 ◽  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
B Lymphocytes ◽  
Complement System ◽  
Chromosome 17 ◽  
T Complex ◽  
Histocompatibility System ◽  
Humoral Antibodies ◽  
Functional Classes ◽  
The Complement System

The H-2 system is a complex of at least ten loci carried by chromosome 17 of the mouse. The loci can be divided into three or four functional classes concerned with the control and execution of immune response. The different classes are in some specific way involved in: 1. differentiation of bone-marrow derived (B) lymphocytes, leading to the production of humoral antibodies detectable by serological methods; 2. differentiation of thymus-derived (T) lymphocytes, leading to the production of killer cells capable of specifically attacking relevant targets; 3. regulation of immune response, both humoral and cellular (this response can be either enhanced or suppressed); 4. biosynthesis and activation of components of the complement system. On the same chromosome as the H-2 is the T/t complex, which controls embryonic and spermatozoal differentiation. An interesting relation between H-2 and T/t might exist between the complexes of loci.

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