scholarly journals Putative GTPase GIMAP1 is critical for the development of mature B and T lymphocytes

Blood ◽  
2010 ◽  
Vol 115 (16) ◽  
pp. 3249-3257 ◽  
Author(s):  
Amy Saunders ◽  
Louise M. C. Webb ◽  
Michelle L. Janas ◽  
Amanda Hutchings ◽  
John Pascall ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Conditional Knockout ◽  
Lymphocyte Development ◽  
Single Positive ◽  
Mature Lymphocyte ◽  
Knockout Allele ◽  
B And T Lymphocytes

Abstract The guanosine triphosphatases (GTPases) of the immunity-associated protein (GIMAP) family of putative GTPases has been implicated in the regulation of T-lymphocyte development and survival. A mouse conditional knockout allele was generated for the immune GTPase gene GIMAP1. Homozygous loss of this allele under the influence of the lymphoid-expressed hCD2-iCre recombinase transgene led to severe (> 85%) deficiency of mature T lymphocytes and, unexpectedly, of mature B lymphocytes. By contrast there was little effect of GIMAP1 deletion on immature lymphocytes in either B or T lineages, although in vitro studies showed a shortening of the survival time of both immature and mature CD4+ single-positive thymocytes. These findings show a vital requirement for GIMAP1 in mature lymphocyte development/survival and draw attention to the nonredundant roles of members of the GIMAP GTPase family in these processes.

scholarly journals T lymphocyte-dependent B lymphocyte proliferative response to antigen. I Genetic restriction of the stimulation of B lymphocyte proliferation.

1981 ◽  
Vol 153 (4) ◽  
pp. 871-882 ◽  
Author(s):  
H Y Tse ◽  
J J Mond ◽  
W E Paul
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Lymphocyte Proliferation ◽  
B Lymphocyte ◽  
Antigen Specificity ◽  
Apparent Lack ◽  
The Face ◽  
Stimulation Of

For the purpose of examining more closely the interaction between T and B lymphocytes, we have developed an in vitro T lymphocyte-dependent B lymphocyte proliferation assay. Proliferation of B lymphocytes in response to antigen was found to depend on the presence of primed T lymphocytes; the B lymphocytes could be derived from nonprimed animals. It appears that these B cells were nonspecifically recruited to proliferate. This nonspecific recruitment, however, was found to be Ir-gene restricted in that B lymphocytes from B10.S mice, which are genetic nonresponders to the polymer Glu60-Ala30-Tyr10 (GAT), could not be stimulated by GAT-primed (responder X nonresponder) F1 T cells. The apparent lack of antigen specificity in the face of Ir gene-restricted T-B interaction may have important implications in our understanding of the recognition unit(s) on T lymphocytes.

A regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes

2021 ◽  
Vol 118 (46) ◽  
pp. e2104297118
Author(s):  
Sameena Nikhat ◽  
Anurupa D. Yadavalli ◽  
Arpita Prusty ◽  
Priyanka K. Narayan ◽  
Dasaradhi Palakodeti ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Lymphocytes ◽  
Cell Fate ◽  
T Lymphocyte ◽  
De Novo ◽  
Gene Expression Pattern ◽  
Lymphocyte Development ◽  
Motif Analysis ◽  
Differentiation Potential ◽  
B And T Lymphocytes

The commitment of hematopoietic multipotent progenitors (MPPs) toward a particular lineage involves activation of cell type–specific genes and silencing of genes that promote alternate cell fates. Although the gene expression programs of early–B and early–T lymphocyte development are mutually exclusive, we show that these cell types exhibit significantly correlated microRNA (miRNA) profiles. However, their corresponding miRNA targetomes are distinct and predominated by transcripts associated with natural killer, dendritic cell, and myeloid lineages, suggesting that miRNAs function in a cell-autonomous manner. The combinatorial expression of miRNAs miR-186-5p, miR-128-3p, and miR-330-5p in MPPs significantly attenuates their myeloid differentiation potential due to repression of myeloid-associated transcripts. Depletion of these miRNAs caused a pronounced de-repression of myeloid lineage targets in differentiating early–B and early–T cells, resulting in a mixed-lineage gene expression pattern. De novo motif analysis combined with an assay of promoter activities indicates that B as well as T lineage determinants drive the expression of these miRNAs in lymphoid lineages. Collectively, we present a paradigm that miRNAs are conserved between developing B and T lymphocytes, yet they target distinct sets of promiscuously expressed lineage-inappropriate genes to suppress the alternate cell-fate options. Thus, our studies provide a comprehensive compendium of miRNAs with functional implications for B and T lymphocyte development.

scholarly journals SURFACE MARKERS ON HUMAN B AND T LYMPHOCYTES

1973 ◽  
Vol 138 (6) ◽  
pp. 1365-1378 ◽  
Author(s):  
Mikael Jondal ◽  
George Klein
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
B Lymphocyte ◽  
Surface Markers ◽  
Barr Virus ◽  
Human Peripheral Lymphocytes ◽  
Epstein Barr ◽  
Viral Determinants ◽  
B And T Lymphocytes

Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus (EBV) because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma. This was done by a cytoadherence technique where virus-producing cells, displaying fresh viral determinants in their cytoplasmatic membrane, were mixed with lymphocytes. Unfractionated lymphocytes were found to adhere to these cells in contrast to column-purified T lymphocytes. The specificity of the binding was confirmed by blocking experiments that showed that sera containing high titers of antibodies directed against the virus could partially inhibit the adherence in contrast to low-titer sera. It is concluded that B lymphocytes, in contrast to T lymphocytes, have receptors for EBV. In a second line of experiments it was found that established human lymphoblastoid lines that carry the EBV genome had receptors characteristic for B lymphocytes and did not form T-lymphocyte rosettes. In contrast, a line of known T-lymphocyte origin that did not carry the EBV genome had receptors characteristic for T lymphocytes. EBV-transformed simian lymphoblastoid lines had surface markers indicating a B-lymphocyte origin in contrast to HVS-transformed simian lines that lacked surface immunoglobulin but carried receptors for sheep red blood cells.

scholarly journals Impaired V(D)J Recombination and Lymphocyte Development in Core RAG1-expressing Mice

2003 ◽  
Vol 198 (9) ◽  
pp. 1439-1450 ◽  
Author(s):  
Darryll D. Dudley ◽  
JoAnn Sekiguchi ◽  
Chengming Zhu ◽  
Moshe J. Sadofsky ◽  
Scott Whitlow ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Lymphocytes ◽  
Lymphocyte Development ◽  
Cell Numbers ◽  
Developmental Progression ◽  
Ordered Assembly ◽  
B And T Lymphocytes

RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated “core” RAG proteins. To identify potential functions for noncore regions and assess functionality of core RAG1 in vivo, we generated core RAG1 knockin (RAG1c/c) mice. Significant B and T cell numbers are generated in RAG1c/c mice, showing that core RAG1, despite missing ∼40% of the RAG1 sequence, retains significant in vivo function. However, lymphocyte development and the overall level of V(D)J recombination are impaired at the progenitor stage in RAG1c/c mice. Correspondingly, there are reduced numbers of peripheral RAG1c/c B and T lymphocytes. Whereas normal B lymphocytes undergo rearrangement of both JH loci, substantial levels of germline JH loci persist in mature B cells of RAG1c/c mice, demonstrating that DJH rearrangement on both IgH alleles is not required for developmental progression to the stage of VH to DJH recombination. Whereas VH to DJH rearrangements occur, albeit at reduced levels, on the nonselected alleles of RAG1c/c B cells that have undergone D to JH rearrangements, we do not detect VH to DH rearrangements in RAG1c/c B cells that retain germline JH alleles. We discuss the potential implications of these findings for noncore RAG1 functions and for the ordered assembly of VH, DH, and JH segments.

β-1,4-mannosyl-glycoprotein β-1,4-N-acetylglucosaminyltransferase III activity in human B and T lymphocyte lines and in tonsillar B and T lymphocytes

1988 ◽  
Vol 66 (8) ◽  
pp. 889-900 ◽  
Author(s):  
S. Narasimhan ◽  
J. W. W. Lee ◽  
R. K. Cheung ◽  
E. W. Gelfand ◽  
H. Schachter
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Lines ◽  
T Lymphocyte ◽  
Proton Nuclear Magnetic Resonance ◽  
Membrane Glycoproteins ◽  
T Cell Lines ◽  
B And T Lymphocytes

β-1,4-mannosyl-glycoprotein β-1,4-N-acetylglucosaminyltransferase III (GlcNAc-T III) catalyzes the incorporation of a "bisecting" N-acetylglucosamine (GlcNAc) residue in β1—4 linkage to the β-linked mannose of the core of asparagine linked–protein bound oligosaccharides (N-glycans). The activity of GlcNAc-T III was determined in Triton X-100 extracts of four human Epstein-Barr virus (EBV)-infected B-cell lines, in four T-cell lines originally established from lymphocytes of patients with acute lymphatic leukemia, and in human tonsillar B and T lymphocytes. The four EBV-transformed B-cell lines showed appreciable GlcNAc-T III activities (ranging from 3.4 to 19.0 nmol∙h−1∙mg protein−1), while the tonsillar resting B lymphocytes had much less activity (0.68 nmol∙h−1∙mg protein−1). The four T-cell lines and the tonsillar T lymphocytes had negligible GlcNAc-T III activities (ranging from 0.02 to 0.25 nmol∙h−1∙mg protein−1). Enzyme product was identified by high resolution proton nuclear magnetic resonance spectroscopy and methylation analysis. This is the first demonstration of GlcNAc-T III activity in human lymphocytes. The presence of GlcNAc-T III in B-cell lines correlates with the reported occurrence of bisecting GlcNAc residues in the oligosaccharides of human immunoglobulins G, A1, M, and D, tonsillar class II antigens, and membrane glycoproteins from B lymphocytes. The negligible GlcNAc-T III activity of the four human T-cell lines and of tonsillar T lymphocytes agrees with the reported absence of bisected structures in N-glycans from human T lymphocyte membrane glycoproteins.

scholarly journals Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 382-388 ◽  
Author(s):  
S D Hearing ◽  
M Norman ◽  
C S J Probert ◽  
N Haslam ◽  
C M Dayan
Keyword(s):  
Ulcerative Colitis ◽  
T Lymphocytes ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Steroid Treatment ◽  
Steroid Resistance ◽  
Severe Ulcerative Colitis ◽  
Steroid Sensitivity

BACKGROUNDUp to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.AIMTo investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes.METHODSEighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured.RESULTSIn vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups.CONCLUSIONSResults suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.

scholarly journals Development of suppressor T lymphocytes for Epstein-Barr virus-induced B-lymphocyte outgrowth during acute infectious mononucleosis: assessment by two quantitative systems

Blood ◽  
1981 ◽  
Vol 57 (3) ◽  
pp. 510-517 ◽  
Author(s):  
RT Schooley ◽  
BF Haynes ◽  
J Grouse ◽  
C Payling-Wright ◽  
AS Fauci ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
B Lymphocytes ◽  
Epstein Barr Virus ◽  
B Lymphocyte ◽  
Acute Stage ◽  
Cell Mediated Immunity ◽  
Barr Virus ◽  
Epstein Barr

Abstract A system of 3H-thymidine incorporation by lymphocytes in culture for 3 wk has been utilized for quantitative assessment of the ability of T lymphocytes to inhibit outgrowth of autologous Epstein-Barr virus (EBV) transformed B lymphocytes. Lymphocytes from EBV-seronegative individuals lack the ability to suppress outgrowth of autologous EBV- transformed B lymphocytes. This capability appears during the course of primary EBV-induced infectious mononucleases (IM) as the atypical lymphocytosis is subsiding and persists for years after recovery from primary EBV infection. The ability of T lymphocytes from EBV- seropositive subjects or convalescent IM patients to inhibit B- lymphocyte outgrowth is not HLA restricted. Thus, T lymphocytes capable of inhibition of in vitro EBV-induced B-cell outgrowth emerge during the acute stage of IM and may represent an important control mechanism of EBV-induced B-lymphocyte proliferation in vivo. The system provides a highly sensitive quantitative means for in vitro assessment of cell- mediated immunity to EBV.

scholarly journals New Predictor of Organ Failure in Acute Pancreatitis: CD4+ T Lymphocytes and CD19+ B Lymphocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Chenyuan Shi ◽  
Chaoqun Hou ◽  
Xiaole Zhu ◽  
Yunpeng Peng ◽  
Feng Guo ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
T Lymphocytes ◽  
Organ Failure ◽  
Clinical Outcomes ◽  
B Lymphocytes ◽  
T Lymphocyte ◽  
Roc Curve ◽  
Scoring Systems ◽  
Gallstone Pancreatitis ◽  
Effector Cells

Objective. Lymphocytes are one of the main effector cells in the inflammatory response of acute pancreatitis (AP). The purpose of the study was to evaluate whether peripheral blood lymphocyte (PBL) subsets at admission change during AP based on clinical outcomes and to explore whether these changes vary by aetiology of AP. Hence, we performed a prospective study to find a predictor in lymphocyte subsets that might allow easier, earlier, and more accurate prediction of clinical outcomes. Methods. Patients with AP were enrolled from December 2017 to June 2018 at the First Affiliated Hospital of Nanjing Medical University. Age, sex, clinical and biochemical parameters, and aetiology of AP were obtained at admission. PBL counts were assessed within 24 hours after admission. Clinical outcomes were observed as endpoints. The areas under the curve (AUCs) of different predictors were calculated using the receiver operating characteristic (ROC) curve. Results. Overall, 133 patients were included. Patients (n=24) with organ failure (OF) had significantly lower CD4+ T lymphocyte levels than those (n=109) with No OF (NOF) (39.60 (33.94-46.13) vs. 32.41 (26.51-38.00), P=0.004). The OF group exhibited significantly higher CD19+ B lymphocytes than the NOF group (16.07 (10.67-21.06) vs. 23.78 (17.84-29.45), P=0.001). Of the AP cases, 68.8% were caused by gallstones; 10.1% were attributed to alcohol; 16.5% were due to hyperlipidaemia; and 4.6% had other causes. Across all aetiologies, a lower CD4+ T lymphocyte level was significantly related to OF (P<0.05). However, CD19+ B lymphocytes were significant only in gallstone pancreatitis (P<0.05). The ROC curve results showed that the AUC values of CD4+T lymphocytes, CD19+ B lymphocytes, and combined CD4+T lymphocytes and CD19+ B lymphocytes were similar to those of traditional scoring systems, such as APACHEII and Ranson. Conclusions. CD4+ T and CD19+ B lymphocytes during the early phase of AP can predict OF.

Sign in / Sign up

Export Citation Format

Share Document