scholarly journals Clearance of the SARS-CoV-2 Virus in an Immunocompromised Patient Mediated by Convalescent Plasma without B-Cell Recovery

2021 ◽  
Vol 22 (16) ◽  
pp. 8902
Author(s):  
Maamoun Basheer ◽  
Elias Saad ◽  
Orly Laskar ◽  
Ofir Schuster ◽  
Hagai Rechnitzer ◽  
...  
Keyword(s):  
Case Report ◽  
Immune System ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
B Lymphocyte ◽  
Immunocompromised Patient ◽  
Population Recovery ◽  
Cell Recovery ◽  
Combined Use

Coronavirus disease (COVID-19) is a contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This case report presents a patient who had difficulty eradicating the corona virus due to being treated with Rituximab, which depletes B lymphocyte cells and therefore disables the production of neutralizing antibodies. The combined use of external anti-viral agents like convalescent plasma, IVIG and Remdesivir successfully helped the patient’s immune system to eradicate the virus without B-cell population recovery. In vitro studies showed that convalescent plasma is the main agent that helped in eradicating the virus.

Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro

1992 ◽  
Vol 12 (2) ◽  
pp. 518-530
Author(s):  
R Palacios ◽  
J Samaridis
Keyword(s):  
B Cell ◽  
B Lymphocytes ◽  
Stromal Cells ◽  
B Lymphocyte ◽  
Germ Line ◽  
Fetal Liver ◽  
Rag 1 ◽  
B Cell Precursors

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.

scholarly journals Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 824-829
Author(s):  
BS Wilson ◽  
JL Platt ◽  
NE Kay
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Human Peripheral Blood ◽  
Raji Cell ◽  
Lymphoid Cells ◽  
Humoral Immune

Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H- thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response.

scholarly journals Attenuation of Apoptosis Underlies B Lymphocyte Stimulator Enhancement of Humoral Immune Response

2000 ◽  
Vol 192 (7) ◽  
pp. 953-964 ◽  
Author(s):  
Richard K.G. Do ◽  
Eunice Hatada ◽  
Hayyoung Lee ◽  
Michelle R. Tourigny ◽  
David Hilbert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
B Lymphocyte ◽  
Humoral Immune ◽  
B Cell Survival ◽  
B Lymphocyte Stimulator

B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.

Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases

1992 ◽  
Vol 12 (5) ◽  
pp. 2315-2321
Author(s):  
M A Campbell ◽  
B M Sefton
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tyrosine Kinases ◽  
B Lymphocyte ◽  
Protein Tyrosine Kinases ◽  
Cell Type ◽  
Protein Tyrosine ◽  
Membrane Immunoglobulin ◽  
Family Protein

Treatment of B lymphocytes with antibodies to membrane immunoglobulin (Ig) stimulates protein tyrosine phosphorylation. We have examined the phosphorylation in vitro of proteins associated with membrane Ig. The Src family protein tyrosine kinases p53/56lyn, p59fyn, and p56lck are associated with membrane Ig in spleen B cells and B-cell lines and undergo phosphorylation in vitro. The pattern of expression of Src family protein tyrosine kinases in B cells varied. Our studies suggest that multiple kinases can potentially interact with membrane Ig and that within any one B-cell type, all of the Src family kinases expressed can be found in association with membrane Ig. We also observed that the Ig-associated Ig alpha protein, multiple forms of Ig beta, and proteins of 100 and 25 kDa were tyrosine phosphorylated in vitro. The 100- and 25-kDa proteins remain unidentified.

Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2973-2979 ◽  
Author(s):  
Anne J. Novak ◽  
Richard J. Bram ◽  
Neil E. Kay ◽  
Diane F. Jelinek
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles

2019 ◽  
Vol 4 (41) ◽  
pp. eaay6125 ◽  
Author(s):  
Velislava N. Petrova ◽  
Bevan Sawatsky ◽  
Alvin X. Han ◽  
Brigitta M. Laksono ◽  
Lisa Walz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cell ◽  
Measles Virus ◽  
B Lymphocyte ◽  
Human Peripheral Blood ◽  
Herd Immunity ◽  
Peripheral Blood Lymphocytes ◽  
Immune Memory ◽  
Virus Challenge

Measles is a disease caused by the highly infectious measles virus (MeV) that results in both viremia and lymphopenia. Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections. Animal models and in vitro studies have proposed various immunological factors underlying this prolonged immune impairment, but the precise mechanisms operating in humans are unknown. Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. Using a surrogate model of measles in ferrets, we investigated the clinical consequences of morbillivirus infection and demonstrated a depletion of vaccine-acquired immunity to influenza virus, leading to a compromised immune recall response and increased disease severity after secondary influenza virus challenge. Our results show that MeV infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease and thus contribute to compromised immunity to previous infections or vaccinations. This work highlights the importance of MeV vaccination not only for the control of measles but also for the maintenance of herd immunity to other pathogens, which can be compromised after MeV infection.

scholarly journals IgG subclass, IgE, and IgA anti-trinitrophenyl antibody production within trinitrophenyl-Ficoll-responsive B cell clones. Evidence in support of three distinct switching pathways.

1983 ◽  
Vol 157 (1) ◽  
pp. 69-85 ◽  
Author(s):  
P K Mongini ◽  
W E Paul ◽  
E S Metcalf
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Igg Subclasses ◽  
Igg Subclass ◽  
Cell Clones ◽  
High Propensity ◽  
Focus Assay

The IgM, IgG subclass, IgE, and IgA anti-trinitrophenyl (TNP) antibody (Ab) response of B cells to the type 2 antigen TNP-Ficoll was studied in athymic nude mice and in the in vitro splenic focus assay. Results from the splenic focus assay in which purified B lymphocyte preparations had been transferred to irradiated nu/nu recipients indicate that many TNP-Ficoll stimulated B cell clones secrete multiple isotypes and hence appear to be undergoing intraclonal isotype switching. Although the frequency of clones secreting each of the IgG subclasses was found to correlate with 5' to 3' Igh-gamma gene order, the frequency of IgE and IgA-secreting clones did not appear to be influenced by the respective position of Igh-epsilon and Igh-alpha on the chromosome. Unlike clones that secreted anti-TNP Ab of the IgG subclasses, IgE and IgA anti-TNP Ab-secreting clones did not have a high propensity for coexpression of isotypes encoded by 5' Igh-C genes. These data suggest that three distinct switching pathways may be employed by B cells responding to TNP-Ficoll: a common IgG pathway, an IgE pathway, and an IgA pathway. The presence of T cells resulted in a preferential enhancement of the production of anti-TNP Ab of those IgG subclasses which were least represented in the absence of T cells, i.e., IgG2b and IgG2a. No significant enhancement of IgE anti-TNP clonal frequency was found in the presence of T lymphocytes, but T cells were found to significantly enhance the clonal expression of IgA anti-TNP Ab. Although a relatively large number of B cell clones were found to synthesize IgE and IgA anti-TNP Ab in the splenic focus assay, relatively little or no secretion of these isotypes was detected in immune mice. Possible explanations for this apparent discrepancy are discussed.

scholarly journals Covalent Linkage of HIV-1 Trimers to Synthetic Liposomes Elicits Improved B Cell and Antibody Responses

2017 ◽  
Vol 91 (16) ◽  
Author(s):  
Shridhar Bale ◽  
Geraldine Goebrecht ◽  
Armando Stano ◽  
Richard Wilson ◽  
Takayuki Ota ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
Neutralizing Antibodies ◽  
Tier 2 ◽  
Covalent Linkage ◽  
His Tag ◽  
Hiv 1

ABSTRACT We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation, and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimers via their C-terminal polyhistidine tails to nickel lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remained over the potentially longer-term in vivo instability of noncovalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the polyhistidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage. Both cobalt and cysteine coupling resulted in a high-density array of NFL trimers that was stable in both 20% mouse serum and 100 mM EDTA, whereas the nickel-conjugated trimers were not stable under these conditions. Binding analysis and calcium flux with anti-Env-specific B cells confirmed that the trimers maintained conformational integrity following coupling. Following immunization of mice, serologic analysis demonstrated that the covalently coupled trimers elicited Env-directed antibodies in a manner statistically significantly improved compared to soluble trimers and nickel-conjugated trimers. Importantly, the covalent coupling not only enhanced gp120-directed responses compared to soluble trimers, it also completely eliminated antibodies directed to the C-terminal His tag located at the “bottom” of the spike. In contrast, soluble and noncovalent formats efficiently elicited anti-His tag antibodies. These data indicate that covalent linkage of well-ordered trimers to liposomes in high-density array displays multiple advantages in vitro and in vivo. IMPORTANCE Enveloped viruses typically encode a surface-bound glycoprotein that mediates viral entry into host cells and is a primary target for vaccine design. Liposomes with modified lipid head groups have a unique feature of capturing and displaying antigens on their surfaces, mimicking the native pathogens. Our first-generation nickel-based liposomes captured HIV-1 Env glycoprotein trimers via a noncovalent linkage with improved efficacy over soluble glycoprotein in activating germinal center B cells and eliciting tier-2 autologous neutralizing antibodies. In this study, we report the development of second-generation cobalt- and maleimide-based liposomes that have improved in vitro stability over nickel-based liposomes. In particular, the maleimide liposomes captured HIV-1 Env trimers via a more stable covalent bond, resulting in enhanced germinal center B cell responses that generated higher antibody titers than the soluble trimers and liposome-bearing trimers via noncovalent linkages. We further demonstrate that covalent coupling prevents release of the trimers prior to recognition by B cells and masks a nonneutralizing determinant located at the bottom of the trimer.

scholarly journals TACI-BLyS signaling via B-cell–dendritic cell cooperation is required for naive CD8+ T-cell priming in vivo

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 594-601 ◽  
Author(s):  
Yaiza Diaz-de-Durana ◽  
George T. Mantchev ◽  
Richard J. Bram ◽  
Alessandra Franco
Keyword(s):  
B Cells ◽  
Dendritic Cell ◽  
B Cell ◽  
B Lymphocyte ◽  
Costimulatory Molecule ◽  
Early Signal ◽  
Maturation In Vitro ◽  
Deficient Mice

AbstractWe demonstrated that B-cell–dendritic cell (DC) interactions via transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequate numbers of mature antigen presenting cells (APCs) to prime naive CD8+ T cells (CTLs) in vivo. Evidence that B cells are required for efficient CTL generation in mice and that reconstitution with wild-type but not TACI-knockout B cells restored normal CTL responses support our conclusion. Moreover, low doses of a TACI fusion protein (TACI-Fc) that express the extracellular domain of TACI (amino acid [aa] 1-126) restored CTL priming in B-cell–deficient mice in vivo and induced DC maturation in vitro. In fact, following interactions with B cells, splenic DCs rapidly express the CD86 costimulatory molecule, to an extent comparable to the exposure to antigenic stimuli. BLyShigh peptide-pulsed bone marrow–derived DCs, used as vaccines in vivo, cannot generate CTLs in B-cell–deficient and TACI-deficient mice, strongly supporting a need for B-cell–DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.

scholarly journals Loss of the Pro-Apoptotic BH3-only Bcl-2 Family Member Bim Inhibits BCR Stimulation–induced Apoptosis and Deletion of Autoreactive B Cells

2003 ◽  
Vol 198 (7) ◽  
pp. 1119-1126 ◽  
Author(s):  
Anselm Enders ◽  
Philippe Bouillet ◽  
Hamsa Puthalakath ◽  
Yuekang Xu ◽  
David M. Tarlinton ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Family Member ◽  
B Lymphocyte ◽  
Survival Function ◽  
Autoreactive B Cells ◽  
Induced Apoptosis ◽  
Self Antigen

During development, the stochastic process assembling the genes encoding antigen receptors invariably generates B and T lymphocytes that can recognize self-antigens. Several mechanisms have evolved to prevent the activation of these cells and the concomitant development of autoimmune disease. One such mechanism is the induction of apoptosis in developing or mature B cells by engagement of the B cell antigen receptor (BCR) in the absence of T cell help. Here we report that B lymphocytes lacking the pro-apoptotic Bcl-2 family member Bim are refractory to apoptosis induced by BCR ligation in vitro. The loss of Bim also inhibited deletion of autoreactive B cells in vivo in two transgenic systems of B cell tolerance. Bim loss prevented deletion of autoreactive B cells induced by soluble self-antigen and promoted accumulation of self-reactive B cells developing in the presence of membrane-bound self-antigen, although their numbers were considerably lower compared with antigen-free mice. Mechanistically, we determined that BCR ligation promoted interaction of Bim with Bcl-2, inhibiting its survival function. These findings demonstrate that Bim is a critical player in BCR-mediated apoptosis and in B lymphocyte deletion.

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