scholarly journals Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation

2021 ◽  
Vol 218 (6) ◽  
Author(s):  
Rahul Vijay ◽  
Jenna J. Guthmiller ◽  
Alexandria J. Sturtz ◽  
Sequoia Crooks ◽  
Jordan T. Johnson ◽  
...  
Keyword(s):  
Cell Activation ◽  
Parasite Burden ◽  
B Cell Activation ◽  
Plasmodium Parasite ◽  
Rbc Membrane ◽  
Phosphatidylserine Exposure ◽  
Phosphatidylserine Receptor ◽  
Infected Rbcs ◽  
And Function

Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite–infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.

NFATc3 regulates the transcription of genes involved in T-cell activation and angiogenesis

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 795-803 ◽  
Author(s):  
Katia Urso ◽  
Arantzazu Alfranca ◽  
Sara Martínez-Martínez ◽  
Amelia Escolano ◽  
Inmaculada Ortega ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Target Genes ◽  
Gene Knockout ◽  
Activated T Cells ◽  
Knock Down ◽  
And Function

Abstract The nuclear factor of activated T cells (NFAT) family of transcription factors plays important roles in many biologic processes, including the development and function of the immune and vascular systems. Cells usually express more than one NFAT member, raising the question of whether NFATs play overlapping roles or if each member has selective functions. Using mRNA knock-down, we show that NFATc3 is specifically required for IL2 and cyclooxygenase-2 (COX2) gene expression in transformed and primary T cells and for T-cell proliferation. We also show that NFATc3 regulates COX2 in endothelial cells, where it is required for COX2, dependent migration and angiogenesis in vivo. These results indicate that individual NFAT members mediate specific functions through the differential regulation of the transcription of target genes. These effects, observed on short-term suppression by mRNA knock-down, are likely to have been masked by compensatory effects in gene-knockout studies.

scholarly journals Expression of Inducible Nitric Oxide Synthase in Skin Lesions of Patients with American Cutaneous Leishmaniasis

2002 ◽  
Vol 70 (8) ◽  
pp. 4638-4642 ◽  
Author(s):  
Muna Qadoumi ◽  
Inge Becker ◽  
Norbert Donhauser ◽  
Martin Röllinghoff ◽  
Christian Bogdan
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Skin Lesions ◽  
And Function ◽  
Oxide Synthase

ABSTRACT Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis that the expression of iNOS was most prominent in LCL lesions with small numbers of parasites whereas lesions with a high parasite burden (LCL or DCL) contained considerably fewer iNOS-positive cells. This is the first study to suggest an antileishmanial function of iNOS in human Leishmania infections in vivo.

scholarly journals APRIL-Deficient Mice Have Normal Immune System Development

2004 ◽  
Vol 24 (3) ◽  
pp. 997-1006 ◽  
Author(s):  
Eugene Varfolomeev ◽  
Frank Kischkel ◽  
Flavius Martin ◽  
Dhaya Seshasayee ◽  
Hua Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
System Development ◽  
Physiological Role ◽  
B Cell Activation ◽  
Tnf Superfamily ◽  
Immune System Development ◽  
Humoral Responses

ABSTRACT APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL−/− mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.

scholarly journals Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation.

1982 ◽  
Vol 155 (5) ◽  
pp. 1385-1399 ◽  
Author(s):  
M Goldman ◽  
L M Rose ◽  
A Hochmann ◽  
P H Lambert
Keyword(s):  
B Cell ◽  
Immune Complexes ◽  
Cell Activation ◽  
Fluorescein Isothiocyanate ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Myeloma Protein ◽  
B Cell Repertoire ◽  
Glomerular Lesions

We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC-15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions.

scholarly journals In vivo Effects of Romidepsin on T-Cell Activation, Apoptosis and Function in the BCN02 HIV-1 Kick&Kill Clinical Trial

2020 ◽  
Vol 11 ◽  
Author(s):  
Miriam Rosás-Umbert ◽  
Marta Ruiz-Riol ◽  
Marco A. Fernández ◽  
Marta Marszalek ◽  
Pep Coll ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
And Function ◽  
In Vivo Effects ◽  
Hiv 1

scholarly journals Tumor-Related Exosomes Contribute to Tumor-Promoting Microenvironment: An Immunological Perspective

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Wuzhen Chen ◽  
Jingxin Jiang ◽  
Wenjie Xia ◽  
Jian Huang
Keyword(s):  
T Cell ◽  
Cell Activation ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Effector T Cell ◽  
T Cell Apoptosis ◽  
And Function

Exosomes are a kind of cell-released membrane-form structures which contain proteins, lipids, and nucleic acids. These vesicular organelles play a key role in intercellular communication. Numerous experiments demonstrated that tumor-related exosomes (TEXs) can induce immune surveillance in the microenvironment in vivo and in vitro. They can interfere with the maturation of DC cells, impair NK cell activation, induce myeloid-derived suppressor cells, and educate macrophages into protumor phenotype. They can also selectively induce effector T cell apoptosis via Fas/FasL interaction and enhance regulatory T cell proliferation and function by releasing TGF-β. In this review, we focus on the TEX-induced immunosuppression and microenvironment change. Based on the truth that TEXs play crucial roles in suppressing the immune system, studies on modification of exosomes as immunotherapy strategies will also be discussed.

Sites of B-cell activation in vivo

1993 ◽  
Vol 5 (3) ◽  
pp. 418-422 ◽  
Author(s):  
Garnett Kelsoe ◽  
Biao Zheng
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Cell Activation

Enhanced B Cell Activation in the Absence of CD81

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2578-2578
Author(s):  
Mrinmoy Sanyal ◽  
Rosemary Fernandez ◽  
Shoshana Levy
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Receptor ◽  
Free Calcium ◽  
B Cell Activation ◽  
Membrane Reorganization ◽  
A Cell

Abstract CD81 is a component of the CD19/CD21 coreceptor complex in B cells. This tetraspanin molecule was previously shown to enable membrane reorganization in B cells responding to complement-bound antigens. Here we stimulated B cells via their B cell receptor (BCR) and demonstrate that Cd81−/− B cells fluxed higher intracellular free calcium ion along with increased phosphorylation of PLCγ2 and Syk. The stimulated Cd81−/− B cells also proliferated faster and secreted higher amounts of antibodies. Moreover, activation of the TLR4 pathway in Cd81−/− B cells induced increased proliferation and antibody secretion. Furthermore, Cd81−/− mice mounted a significantly higher immune response to T-cell independent antigens than their wildtype counterparts. Finally, analysis of Cd81−/− B cells that were generated by bone marrow transplantation into Rag1−/− mice confirmed a cell intrinsic hyperactive phenotype. Taken together, these results indicate that CD81 plays a negative role in B cell activation in vitro and in vivo.

Sign in / Sign up

Export Citation Format

Share Document