scholarly journals Murine gammaherpesvirus M2 antigen modulates splenic B cell activation and terminal differentiation in vivo

2017 ◽  
Vol 13 (8) ◽  
pp. e1006543 ◽  
Author(s):  
Shariya Terrell ◽  
Samuel H. Speck
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Terminal Differentiation ◽  
B Cell Activation ◽  
Murine Gammaherpesvirus

scholarly journals Signaling through Toll-Like Receptors Induces Murine Gammaherpesvirus 68 Reactivation In Vivo

2008 ◽  
Vol 83 (3) ◽  
pp. 1474-1482 ◽  
Author(s):  
Lisa M. Gargano ◽  
J. Craig Forrest ◽  
Samuel H. Speck
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Toll Like Receptors ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68 ◽  
Stimulation Of

ABSTRACT Murine gammaherpesvirus 68 (MHV68) establishes a lifelong infection in mice and is used as a model pathogen to study the role of viral and host factors in chronic infection. The maintenance of chronic MHV68 infection, at least in some latency reservoirs, appears to be dependent on the capacity of the virus to reactivate from latency in vivo. However, the signals that lead to MHV68 reactivation in vivo are not well characterized. Toll-like receptors (TLRs), by recognizing the specific patterns of microbial components, play an essential role in the activation of innate immunity. In the present study, we investigated the capacity of TLR ligands to induce MHV68 reactivation, both in vitro and in vivo. The stimulation of latently infected B cell lines with ligands for TLRs 3, 4, 5, and 9 enhanced MHV68 reactivation; the ex vivo stimulation of latently infected primary splenocytes, recovered from infected mice, with poly(I:C), lipopolysaccharide, flagellin, or CpG DNA led to early B-cell activation, B-cell proliferation, and a significant increase in the frequency of latently infected cells reactivating the virus. In vivo TLR stimulation also induced B-cell activation and MHV68 reactivation, resulting in heightened levels of virus replication in the lungs which correlated with an increase in MHV68-specific CD8+ T-cell responses. Importantly, TLR stimulation also led to an increase in MHV68 latency, as evidenced by an increase in viral genome-positive cells 2 weeks post-in vivo stimulation by specific TLR ligands. Thus, these data demonstrate that TLR stimulation can drive MHV68 reactivation from latency and suggests that periodic pathogen exposure may contribute to the homeostatic maintenance of chronic gammaherpesvirus infection through stimulating virus reactivation and reseeding latency reservoirs.

scholarly journals Non-Antigen-Specific B-Cell Activation following Murine Gammaherpesvirus Infection Is CD4 Independent In Vitro but CD4 Dependent In Vivo

1999 ◽  
Vol 73 (2) ◽  
pp. 1075-1079 ◽  
Author(s):  
Philip G. Stevenson ◽  
Peter C. Doherty
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Total Serum ◽  
B Cell Activation ◽  
Murine Gammaherpesvirus ◽  
Vitro Effect

ABSTRACT The murine gammaherpesvirus MHV-68 multiplies in the respiratory epithelium after intranasal inoculation, then spreads to infect B cells in lymphoid germinal centers. Exposing B cells to MHV-68 in vitro caused an increase in cell size, up-regulation of the CD69 activation marker, and immunoglobulin M (IgM) production. The infectious process in vivo was also associated with increased CD69 expression on B cells in the draining lymph nodes and spleen, together with a rise in total serum Ig. However, whereas the in vitro effect on B cells was entirely T-cell independent, evidence of in vivo B-cell activation was minimal in CD4+ T-cell-deficient (I-Ab−/−) or CD4+ T-cell-depleted mice. Furthermore, the Ig present at high levels in serum was predominantly of the IgG class. Surprisingly, the titer of influenza virus-specific serum IgG in previously immunized mice fell following MHV-68 infection, suggesting that there was relatively little activation of memory B cells. Thus, CD4+T cells seemed both to amplify a direct viral activation of B cells in lymphoid tissue and to promote new Ig class switching despite a lack of obvious cognate antigen.

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.

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.

scholarly journals An IRF4-MYC-mTORC1 integrated pathway controls cell growth and the proliferative capacity of activated B cells during B cell differentiation in vivo

2021 ◽  
Author(s):  
Dillon G Patterson ◽  
Anna K Kania ◽  
Madeline J Price ◽  
James R Rose ◽  
Christopher D Scharer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
B Cells ◽  
Cell Growth ◽  
B Cell ◽  
Proliferative Response ◽  
Cell Activation ◽  
B Cell Differentiation ◽  
B Cell Activation

Cell division is an essential component of B cell differentiation to antibody-secreting plasma cells, with critical reprogramming occurring during the initial stages of B cell activation. However, a complete understanding of the factors that coordinate early reprogramming events in vivo remain to be determined. In this study, we examined the initial reprogramming by IRF4 in activated B cells using an adoptive transfer system and mice with a B cell-specific deletion of IRF4. IRF4-deficient B cells responding to influenza, NP-Ficoll and LPS divided, but stalled during the proliferative response. Gene expression profiling of IRF4-deficient B cells at discrete divisions revealed IRF4 was critical for inducing MYC target genes, oxidative phosphorylation, and glycolysis. Moreover, IRF4-deficient B cells maintained an inflammatory gene expression signature. Complementary chromatin accessibility analyses established a hierarchy of IRF4 activity and identified networks of dysregulated transcription factor families in IRF4-deficient B cells, including E-box binding bHLH family members. Indeed, B cells lacking IRF4 failed to fully induce Myc after stimulation and displayed aberrant cell cycle distribution. Furthermore, IRF4-deficient B cells showed reduced mTORC1 activity and failed to initiate the B cell-activation unfolded protein response and grow in cell size. Myc overexpression in IRF4-deficient was sufficient to overcome the cell growth defect. Together, these data reveal an IRF4-MYC-mTORC1 relationship critical for controlling cell growth and the proliferative response during B cell differentiation.

scholarly journals Inhibition of Fcγ Receptor-Mediated Phagocytosis by a Nonphagocytic Fcγ Receptor

Blood ◽  
1998 ◽  
Vol 91 (5) ◽  
pp. 1762-1768 ◽  
Author(s):  
Sharon Hunter ◽  
Zena K. Indik ◽  
Moo-Kyung Kim ◽  
M. Danielle Cauley ◽  
Jong-Gu Park ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cytoplasmic Domain ◽  
Inhibitory Effect ◽  
B Cell Antigen Receptor ◽  
B Cell Activation ◽  
Fcγ Receptor ◽  
Γ Subunit ◽  
Molecular Events

There are three major classes of human Fcγ receptors (FcγRI, FcγRII, and FcγRIII) and various isoforms of each class are capable of mediating phagocytosis. FcγRIIA is an unusual Fcγ receptor in that it transmits a phagocytic signal in the absence of an additional receptor subunit. The cytoplasmic domain of FcγRIIA contains a conserved motif containing two copies of the sequence YXXL. The tyrosines (Y) within the motif are phosphorylated after receptor crosslinking and the integrity of these conserved sequences is required for efficient phagocytosis. The FcγRIIB receptors, FcγRIIB1 and FcγRIIB2, contain one copy of the cytoplasmic YXXL sequence and do not transmit a phagocytic signal. In B cells, FcγRIIB negatively regulates B-cell activation by the B-cell antigen receptor. Human macrophages express both FcγRIIA and FcγRIIB and while FcγRIIA mediates phagocytosis, the function of FcγRIIB in these cells is unknown. Using the epithelial/fibroblast-like cell line COS-1 as a model to examine the molecular events that regulate the phagocytosis of IgG-coated cells (EA), we investigated the effect of FcγRIIB on FcγRIIA signaling. FcγRIIB inhibited phagocytosis mediated both by FcγRIIA and by a chimeric FcγRIIA receptor containing the extracellular domain of FcγRI and the transmembrane and cytoplasmic domains of FcγRIIA. This inhibition occurred at an early signaling stage because tyrosine phosphorylation of the FcγRIIA cytoplasmic domain was inhibited after concurrent stimulation of these receptors with EA. FcγRIIB mutations showed the importance of the FcγRIIB YXXL for inhibition of FcγRIIA-mediated phagocytosis. Deletion of the FcγRIIB YXXL or conservative replacement of the YXXL tyrosine substantially reduced the inhibitory signal. FcγRIIB had a lesser inhibitory effect on phagocytosis by the Fcγ receptor FcγRIIIA, which requires a γ subunit to mediate a phagocytic signal. These results show that FcγRIIB negatively regulates phagocytic signaling by FcγRIIA and suggests that FcγRIIB plays a role in modulating FcγRIIA function in vivo.

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