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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice homozygous for the scid (severe combined immunodeficiency) mutation are generally unable to produce B lymphocytes, a condition attributed to defective rearrangement of immunoglobulin genes in precursor B cells. Some early B-lineage cells are present in the bone marrow (BM), however. In scid mice, we defined three subsets of early progenitor B cells lacking mu heavy chains (pro-B cells) based on the expression of terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein: (a) early pro-B cells (TdT+B220-), (b) intermediate pro-B cells (TdT+B220+), and (c) late pro-B cells (TdT-B220+). Double immunofluorescence labeling of BM cell suspensions has shown normal numbers of early and intermediate pro-B cells, substantially reduced numbers of late pro-B cells, and an absence of pre-B cells and B cells. Early and intermediate pro-B cells accumulated in metaphase in near-normal numbers after intraperitoneal (IP) vincristine administration. B220+ pro-B cells have been localized in BM sections by the binding of intravenously (IV) administered 125I monoclonal antibody (MoAb) 14.8, detected by light and electron microscope radioautography. Many B220+ cells were located peripherally in the bone-lining cell layers associated with stromal reticular cells. More centrally located B220+ cells were frequently associated with macrophages containing prominent cytoplasmic inclusions. Occasional B220+ cells were present in venous sinusoids. These results demonstrate that many pro-B cells in scid mice occupy microenvironments in the BM near the surrounding bone. The pro-B cells maintain normal rates of production during stages of presumptive mu heavy-chain gene rearrangement, apparently unaffected by the absence of a mature B cell pool. Nearly all defective cells then abort at the late pro-B cell stage and are deleted, apparently by macrophages. The findings contribute to models of in vivo differentiation, regulation, localization, and selection of early B-lineage cells in the BM.
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PMID:Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice. 137 84

Pre-B cell lines proliferating for several months on stromal cells in the presence of interleukin 7 (IL-7) were established from fetal liver of (NZB x NZW)F1 mice. They express the B lineage-specific markers PB76, B220, and VpreB, but do not express surface immunoglobulin (sIg). Upon removal of IL-7 from the culture, they differentiate to sIg+ B cells that can then be stimulated by lipopolysaccharide to become IgM-secreting cells. Transfer of these pre-B cell lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900 micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next 3-5 mo. The spleen appears populated with (NZB x NZW)F1-derived pre-B cells, few B cells, and many IgM and/or IgG-producing plasma cells. In contrast, SCID mice populated with pre-B cell lines of normal (C57BL/6 x DBA/2)F1 mouse fetal liver develop normal levels of serum IgM (approximately 100-300 micrograms/ml), almost no detectable levels of IgG, and no plasma cell hyperplasia. The (NZB x NZW)F1 pre-B cell-populated SCID mice contain elevated serum titers of IgG antinuclear autoantibodies, but no retroviral gp70-specific nor erythrocyte-specific autoantibodies. Up to 20% of the SCID mice develop proteinuria as a consequence of IgG deposits in the kidney glomeruli during a 7-mo period of observation. All signs of autoimmune disease seen in these mice are independent of the sex of the SCID host. This experimental system provides a distinction between the disease-determining (NZB x NZW)F1 genes, which are expressed in the B lymphocyte lineage and cause the development of the disease, from those expressed in other cell lineages which only modulate its progression.
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PMID:Development of autoimmune disease in SCID mice populated with long-term "in vitro" proliferating (NZB x NZW)F1 pre-B cells. 140 80

A novel glycoprotein (gp) expressed by stromal cells of peripheral lymphoid tissue has been characterized immunohistochemically, biochemically, and at the molecular level. This molecule, gp38, was identified with a monoclonal antibody (mAb) (clone 8.1.1) previously shown to react with a subpopulation of thymic epithelium. This mAb generated a reticular labeling pattern in medullary and paracortical areas of lymph nodes and in splenic white pulp. At the ultrastructural level, labeling by the 8.1.1 mAb was restricted to fibroblastic reticular stromal cells. Serial sections of lymph node and spleen labeled with anti-CD3, anti-B220, and 8.1.1 mAbs clearly showed that the 8.1.1+ cells were associated with T cell-dependent areas. In severe combined immunodeficiency (SCID) or Nu/Nu mice, splenic white pulp also exhibited reticular labeling with the 8.1.1 mAb in the absence of detectable numbers of T cells, indicating that the appearance of 8.1.1-reactive stromal cells in discrete areas of peripheral lymphoid tissue was T cell independent. The cDNA encoding this stromal cell molecule was cloned by direct expression in COS cells and found to encode a 172 amino acid sequence with the typical features of a type I integral membrane protein. COS cells transfected with the gp38 clone direct the expression of an approximately 38-kD protein that reacts with the 8.1.1 mAb but not with isotype-matched controls. Comparison of the predicted amino acid sequence of 8.1.1 mAb but not with isotype-matched controls. Comparison of the predicted amino acid sequence of 8.1.1 with proteins in the National Biomedical Research Foundation (NBRF) data base showed that gp38 is very closely related to the early response protein OTS-8 obtained from a cDNA library of tumor promoting agent (TPA)-induced murine osteoblastic cell line, MC3T3-E1.
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PMID:Characterization and cloning of a novel glycoprotein expressed by stromal cells in T-dependent areas of peripheral lymphoid tissues. 140 91

Cell lines and clones were established from PB76-positive mouse fetal liver at day 13 and 14 of gestation, which proliferated with division times of a day in serum-substituted cultures under the stimulatory influence of adherent stromal cells and the cytokine IL-7 for periods longer than half a year. These lines expressed varying levels of the B lymphocyte lineage related markers PB76, B220, BP-1, VpreB and lambda 5, but no surface Ig or MHC class II molecules. All clones expressed PB76, VpreB and lambda 5 in a high percentage of cells, while B220 and/or BP-1 expression was low or undetectable in some. A cell line, and several clones established from it, all had kappa and lambda light chain genes in germ-line configuration. Either one or both of their H-chain-gene containing chromosomes carried a DH to JH. These pre B cell lines and clones could be induced to VH to DH and VL to JL rearrangements. This resulted in the development of varying percentages of sIg-positive surface, MHC class II negative, LPS-reactive B cells within 2-3 days, in the absence of contacts with stromal cells and/or IL-7. When injected into SCID mice, the cultured pre B cells populated the spleen of these mice to 5% with surface Ig-, MHC class II-positive LPS-reactive cells for greater than 25 weeks. The long-term in vitro proliferative capacity of these DH-JH rearranged pre B cell clones makes them major candidates for committed stem cells of the B lineage.
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PMID:Long-term proliferating early pre B cell lines and clones with the potential to develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo. 199 49

The BP-1/6C3 molecule expressed by early B lineage cells and some stromal cells is a type II integral membrane glycoprotein that belongs to the zinc-dependent family of metallopeptidases. In order to explore the potential role of this cell surface molecule in precursor B cell proliferation, we established a stromal cell line (BHM) from long-term bone marrow cultures of the Whitlock - Witte type and developed a rapid bioassay for the detection of responsive target cells. When non-adherent bone marrow cells were cultured with BHM stroma, we observed an up-regulation of BP-1 expression by the B cell precursors that coincided with the induction of proliferation. The precursor B-cell targets included bone marrow cells that lacked detectable BP-1/6C3, B220, and Ia antigens. They could be identified in fetal liver and in the bone marrow, but not the thymus, spleen, or lymph nodes, of normal BALB/c mice, and were also present in the bone marrow of mice with the nu/nu, CBA/N, and SCID defects. Because the inductive effects on precursor B cells could be reproduced with BHM supernatant, soluble growth factors were evaluated in the assay. Interleukin 7 (IL-7) appeared to be unique in its ability to induce BP-1/6C3 expression and concomitant cell growth. Northern blot analysis revealed that the BHM stromal cells, which themselves express the BP-1 antigen, constitutively expressed high levels of variable length transcripts for IL-7. The data suggest that the IL-7 product of stromal cells selectively induces BP-1/6C3 expression on B cell precursors and may implicate this cell surface glycoprotein in the control of IL-7 induced proliferation of early B lineage cells.
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PMID:Bone marrow stromal cells and interleukin-7 induce coordinate expression of the BP-1/6C3 antigen and pre-B cell growth. 208 32

We have used 3 color FACS analysis (together with dead cell exclusion by propidium iodide) to ascertain the levels of lymphoid lineage cells present in typical young adult (2-5 month) SCID mice. Both mature and early B and T lineage cells are severely decreased (greater than 100X) in thymus, spleen and peritoneum of such mice. Analysis revealed a significant fraction of B220+ cells in bone marrow and, curiously, all such cells co-expressed a determinant recognized by the S7 antibody, likely lost early in B lineage differentiation. Thus, together with B220, expression of S7 may serve to mark the stage at which the SCID defect first becomes manifest, at least in the B lineage. This suggests that B220+/S7+ cells in bone marrow may be pro-B cells or even a lymphoid progenitor population.
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PMID:Analysis of lymphoid population in scid mice; detection of a potential B lymphocyte progenitor population present at normal levels in scid mice by three color flow cytometry with B220 and S7. 247 39

The analysis of the expression of the alpha chain of the IL-2 receptor (CD25, TAC) on the surface of B lineage cells in mouse bone marrow reveals that it is a useful marker to distinguish pre-B-I from pre-B-II cells. CD25 is not expressed on CD45R(B220)+ c-kit+ CD43+ TdT+ lambda 5+ c mu- sIg-IgH chain locus DJH-rearranged pre-B-I cells of mouse bone marrow. It is expressed on large cycling CD45R(B220)+ c-kit- CD43+ TdT- lambda 5+ c mu+ sIg- and on small resting CD45R(B220)+ c-kit- CD43- TdT- lambda 5- c mu- sIg- IgH chain locus VHDJH-rearranged pre-B-II cells. Therefore, the transition from pre-B-I to large pre-B-II cells is marked by the downregulation of c-kit and terminal deoxynucleotidyl transferase (TdT), and by the upregulation of CD25. SCID, RAG-2T, microMT and lambda 5T mutant mice do have normal, if not elevated numbers of pre-B-I cells but lack all CD25+ pre-B-II cells in their bone marrow. The expression of a transgenic H chain under control of the microH chain enhancer in RAG-2T bone marrow B lineage precursors allows the development of large and small CD25+ pre-B-II cells. The results suggest that the differentiation of pre-B-I to pre-B-II cells in mouse bone marrow requires the expression of microH chains and surrogate L chains in membranes, probably on the surface of precursor B cells.
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PMID:IL-2 receptor alpha chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. 752 94

Bovine lymphoid cells were engrafted into untreated and into sublethally irradiated scid/scid mice, following intraperitoneal (i.p.) injection of bovine peripheral blood leukocytes (PBL). To distinguish bovine from murine cells, bovine PBL were stained prior to i.p. injection with a fluorescent cell linker compound, PKH26-GL and, after cell recovery, labelled with a monoclonal antibody (mAb) reactive with the bovine pan leukocyte cell surface marker, CD45, and analyzed by flow cytometry. This dual labelling system was used to monitor tissue localization and migration of bovine cells within PBL-SCID-bo from 30 min to 64 days after bovine PBL injection. Inoculated bovine PBL were rapidly cleared from the peritoneal cavity of PBL-SCID-bo over the first 24 h after injection, then bovine cell numbers within the peritoneal cavity increased gradually over the next 35 days. No bovine cells were observed in the peritoneal wash from either non-irradiated or irradiated mice after Day 56. Bovine cells were detected in the spleens of both non-irradiated and irradiated mice 12-14 days after inoculation, but were undetectable in non-irradiated and irradiated mice after Day 56, and in irradiated mice after Day 35. This decrease coincided with a significant reduction in both the numbers of bovine cells in the peritoneal cavity, and in the levels of bovine Ig detected in the sera. Bovine IgG and bovine IgM were detected in both normal and irradiated PBL-SCID-bo by 4 days after PBL injection, and remained detectable to 8 weeks after inoculation. T-cells appeared to be the predominant bovine cell population in the spleens. In a small proportion of both normal and irradiated PBL-SCID-bo, spleens three to 20 times the size of a normal SCID mouse spleen were observed. Relatively high levels of bovine cells were detected in the thymuses of some irradiated PBL-SCID-bo. Sporadic, low levels of bovine cells were observed in the mesenteric lymph nodes, peripheral blood, and kidneys of normal and irradiated mice, and in the lungs and livers of non-irradiated but not irradiated PBL-SCID-bo. Sublethal gamma irradiation of SCID recipients appeared to enhance engraftment of bovine cells into the murine spleen and thymus.
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PMID:A study on the engraftment and trafficking of bovine peripheral blood leukocytes in severe combined immunodeficient mice. 825 36

We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.
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PMID:Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop. 887 90

Children presenting with disseminated viral infections should be carefully investigated because they almost invariably have an underlying immunodeficiency. A child is reported who had disseminated cytomegalovirus and a novel form of severe combined immunodeficiency with abnormal expression of the common leucocyte antigen, CD45.
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PMID:Severe combined immunodeficiency with abnormalities in expression of the common leucocyte antigen, CD45. 906 11


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