scholarly journals Immunoglobulin-mediated signal transduction in B cells from CD45-deficient mice.

1996 ◽  
Vol 183 (1) ◽  
pp. 329-334 ◽  
Author(s):  
T Benatar ◽  
R Carsetti ◽  
C Furlonger ◽  
N Kamalia ◽  
T Mak ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Buoyant Density ◽  
Lymphoid Tissues ◽  
B Cell Activation ◽  
Normal Numbers ◽  
Cell Responses ◽  
Deficient Mice

CD45 expression is essential for immunoglobulin (Ig)-mediated B cell activation. Treatments with either anti-Ig or anti-CD45 suggest that CD45 may facilitate early signaling events such as calcium mobilization, and phosphoinositide hydrolyis as well as later events leading to transcription of genes such as c-myc. To examine the role of CD45 more extensively, CD45-deficient mice were generated by disruption of exon 6. Although normal numbers of B cells were found in peripheral lymphoid tissues, CD45-deficient cells failed to proliferate upon IgM crosslinking. In the present study, we demonstrate that the fraction of high buoyant density B cells is reduced while low buoyant density cells are increased. Moreover, there is a significant decline in the number of splenic B cells of the mature IgDhi, IgMlo phenotype. Although both the basal and anti-Ig-induced levels of phosphorylation of Ig-alpha and phospholipase C gamma 2 are indistinguishable from that observed in CD45+ control B cells, a major distinction was found in Ca2+ mobilization. While anti-Ig-induced mobilization of intracellular Ca2+ stores was normal, influx from extracellular sources was abrogated. This finding reveals a novel pathway of regulating B cell responses mediated by CD45.

scholarly journals Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19

1998 ◽  
Vol 188 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Thomas Fehr ◽  
Robert C. Rickert ◽  
Bernhard Odermatt ◽  
Jürgen Roes ◽  
Klaus Rajewsky ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Antibody Responses ◽  
B Cell Activation ◽  
Protein Antigens ◽  
Cell Memory ◽  
B Cell Memory

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.

scholarly journals T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cell Accumulation ◽  
Antigen Presenting ◽  
Deficient Mice

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

Critical Role for CD81 in B Cell Activation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1342-1342
Author(s):  
Mrinmoy Sanyal ◽  
Rosemary Fernandez ◽  
Shoshana Levy
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Function ◽  
Calcium Influx ◽  
Critical Role ◽  
B Cell Lymphoma ◽  
Free Calcium ◽  
B Cell Activation ◽  
Deficient Mice

Abstract CD81 is a component of the CD19/CD21 signaling complex in B cells. CD81 was originally discovered as target of an anti-proliferative antibody in a human B cell lymphoma. However, the exact role of CD81 in B cell function is not known. Here we studied B cells from CD81 knockout mice. We demonstrate that upon BCR induction these B cells flux higher intracellular free calcium ion; increase the phosphorylation of BCR-related proximal and distal substrates and increase their proliferation. Similarly, polyclonal activation of CD81-deficient B cells with LPS induced increased proliferation and antibody secretion. Consistent with these intrinsic B cell capabilities, CD81-deficient mice mounted significantly higher immune response upon antigenic stimulation. In addition, bone marrow perisinusoidal B cells (IgM+IgD+) capable of mounting T-independent immune responses against blood-borne pathogens were over represented in CD81-deficient mice. These cells also displayed increased calcium influx kinetics as splenic B cells and produced higher amounts of antibody after polyclonal stimulation. Taken together, these results suggest that CD81 is involved in suppressing B cell activation.

scholarly journals Extrafollicular B cell activation by marginal zone dendritic cells drives T cell–dependent antibody responses

2012 ◽  
Vol 209 (10) ◽  
pp. 1825-1840 ◽  
Author(s):  
Craig P. Chappell ◽  
Kevin E. Draves ◽  
Natalia V. Giltiay ◽  
Edward A. Clark
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Marginal Zone ◽  
Receptor Expression ◽  
B Cell Activation ◽  
Cell Responses ◽  
B Cell Responses

Dendritic cells (DCs) are best known for their ability to activate naive T cells, and emerging evidence suggests that distinct DC subsets induce specialized T cell responses. However, little is known concerning the role of DC subsets in the initiation of B cell responses. We report that antigen (Ag) delivery to DC-inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)–associated CD8α− DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell–dependent (TD) Ag. DCIR2+ DCs induced rapid up-regulation of multiple B cell activation markers and changes in chemokine receptor expression, resulting in accumulation of Ag-specific B cells within extrafollicular splenic bridging channels as early as 24 h after immunization. Ag-specific B cells primed by DCIR2+ DCs were remarkably efficient at driving naive CD4 T cell proliferation, yet DCIR2-induced responses failed to form germinal centers or undergo affinity maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were included at the time of immunization. These results demonstrate DCIR2+ DCs have a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus define a novel division of labor among splenic DC subsets for B cell activation during humoral immune responses.

scholarly journals Ca2+Signaling in B Cells

2010 ◽  
Vol 10 ◽  
pp. 2254-2264 ◽  
Author(s):  
Taras Lyubchenko
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
B Cell Activation ◽  
B Cell Tolerance ◽  
Immune Synapse ◽  
Intracellular Ca ◽  
Dependent Protein

An increase in intracellular Ca2+concentration is one of the major initial steps in B-cell activation that occurs within minutes after antigen receptor (BCR) engagement. In recent years, significant advances have been made in characterizing molecular mechanisms of Ca2+signaling in lymphocytes, although the majority of work was done on T cells. This mini-review discusses several underexplored areas of Ca2+signaling in B cells: (1) Ca2+signaling in immune synapse and multifaceted Ca2+responses within a single cell, (2) source of Ca2+involved in Ca2+-dependent protein phosphorylation events and the role of store-operated influx, (3) role of BCR coreceptors in Ca2+signaling, and (4) Ca2+signaling and maintenance of B-cell tolerance and clinical significance of Ca2+signaling alterations.

scholarly journals Kaposi's Sarcoma-Associated Herpesvirus Latency Locus Compensates for Interleukin-6 in Initial B Cell Activation

2015 ◽  
Vol 90 (4) ◽  
pp. 2150-2154 ◽  
Author(s):  
Sang-Hoon Sin ◽  
Sun Ah Kang ◽  
Yongbaek Kim ◽  
Anthony Eason ◽  
Kelly Tan ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Interleukin 6 ◽  
Cell Activation ◽  
Marginal Zone ◽  
Kaposi Sarcoma ◽  
B Cell Activation ◽  
Marginal Zone B Cells ◽  
Survival Factor

Interleukin 6 (IL-6) is considered a proliferation and survival factor for B cells. To assess the role of IL-6 in Kaposi sarcoma-associated herpesvirus (KSHV) latency, KSHV latency locus-transgenic mice (referred to as latency mice) lacking IL-6 were evaluated. IL-6−/−latency mice had the same phenotypes as the latency mice, i.e., increased frequency of marginal zone B cells, hyperplasia, and hyperglobulinemia, indicating that the KSHV latency locus, which includes all viral microRNAs (miRNAs), can compensate for lack of IL-6 in premalignant B cell activation.

scholarly journals Effects of Friend Virus Infection and Regulatory T Cells on the Antigen Presentation Function of B Cells

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Tyler C. Moore ◽  
Ronald J. Messer ◽  
Lorena M. Gonzaga ◽  
Jennifer M. Mather ◽  
Aaron B. Carmody ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Cell Activation ◽  
T Cell Responses ◽  
B Cell Activation ◽  
Friend Virus ◽  
Cell Responses

ABSTRACTFriend virus (FV) is a naturally occurring mouse retrovirus that infects dividing cells of the hematopoietic lineage, including antigen-presenting cells (APCs). The infection of APCs by viruses often induces their dysfunction, and it has been shown that FV infection reduces the ability of dendritic cells (DCs) to prime critical CD8+T cell responses. Nonetheless, mice mount vigorous CD8+T cell responses, so we investigated whether B cells might serve as alternative APCs during FV infection. Directex vivoanalysis of B cells from FV-infected mice revealed that infected but not uninfected B cells upregulated expression of the costimulatory molecules CD80, CD86, and CD40, as well as major histocompatibility complex class II (MHC-II) molecules. Furthermore,in vitrostudies showed that, compared to uninfected B cells from the same mice, the FV-infected B cells had significantly enhanced APC function, as measured by their capacity to prime CD8+T cell activation and proliferation. Thus, in contrast to DCs, infection of B cells with FV enhanced their APC capacity and ability to stimulate the CD8+T cell responses essential for virus control. FV infections also induce the activation and expansion of regulatory T cells (Tregs), so it was of interest to determine the impact of Tregs on B cell activation. The upregulation of costimulatory molecule expression and APC function of B cells was even more strongly enhanced byin vivodepletion of regulatory T cells than infection. Thus, Tregs exert potent homeostatic suppression of B cell activation that is partially overcome by FV infection.IMPORTANCEThe primary role of B cells in immunity is considered the production of pathogen-specific antibodies, but another, less-well-studied, function of B cells is to present foreign antigens to T cells to stimulate their activation and proliferation. Dendritic cells (DCs) are considered the most important antigen-presenting cells (APCs) for CD8+T cells, but DCs lose APC function when infected with Friend virus (FV), a model retrovirus of mice. Interestingly, B cells were better able to stimulate CD8+T cell responses when they were infected with FV. We also found that the activation status of B cells under homeostatic conditions was potently modulated by regulatory T cells. This study illustrates an important link between B cell and T cell responses and illustrates an additional mechanism by which regulatory T cells suppress critical T cell responses during viral infections.

scholarly journals B cells discriminate HIV-1 Envelope protein affinities by sensing antigen binding association rates

2022 ◽  
Author(s):  
Md. Alamgir Hossain ◽  
Kara Anasti ◽  
Brian Watts ◽  
Kenneth Cronin ◽  
Advaiti Pai Kane ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Neutralizing Antibody ◽  
Antigen Binding ◽  
B Cell Activation ◽  
Kinetic Rates ◽  
Env Protein ◽  
Hiv 1

HIV-1 Envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant, KD) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD, and whether B cells discriminate between proteins of similar affinities but that bind with different kinetic rates. Here we used a panel of Env proteins and Ramos B cell lines expressing IgM BCRs with specificity for CD4 binding-site broadly neutralizing (bnAb) or a precursor antibody to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD, but on sensing of association rate and a threshold antigen-BCR half-life.

scholarly journals Galectin-9 regulates the threshold of B cell activation and autoimmunity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Logan K Smith ◽  
Kareem Fawaz ◽  
Bebhinn Treanor
Keyword(s):  
B Cell ◽  
Regulatory Network ◽  
Cell Activation ◽  
Critical Role ◽  
Peripheral Tolerance ◽  
B Cell Activation ◽  
Cell Compartment ◽  
Cell Responses ◽  
Self Antigen ◽  
Deficient Mice

Despite the mechanisms of central and peripheral tolerance, the mature B cell compartment contains cells reactive for self-antigen. How these cells are poised not to respond and the mechanisms that restrain B cell responses to low-affinity endogenous antigens are not fully understood. Here, we demonstrate a critical role for the glycan-binding protein galectin-9 in setting the threshold of B cell activation and that loss of this regulatory network is sufficient to drive spontaneous autoimmunity. We further demonstrate a critical role for galectin-9 in restraining not only conventional B-2 B cells, but also innate-like B-1a cells. We show that galectin-9-deficient mice have an expanded population of B-1a cells and increased titers of B-1a-derived autoantibodies. Mechanistically, we demonstrate that galectin-9 regulates BCR and distinct TLR responses in B-1a cells, but not B-1b cells, by regulating the interaction between BCR and TLRs with the regulatory molecules CD5 and CD180, respectively. In the absence of galectin-9, B-1a cells are more readily activated and secrete increased titers of autoantibodies that facilitate autoantigen delivery to the spleen, driving autoimmune responses.

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