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PubMed1997

Impaired Ca2+ mobilization by X-linked agammaglobulinaemia (XLA) B cells in response to ligation of the B cell receptor (BCR).

XLA bone marrow samples were shown to contain B cells expressing IgM, and pre-B cells that express the mu-surrogate light chain (mu psiLC) complex, albeit at a reduced frequency to that found in normal bone marrow. Antibody ligation of mu heavy chain on these cells and an XLA B cell line did not induce a Ca2+ flux, whereas ligation of mu heavy chain on normal bone marrow cells, mu psiLC+ pre-B cell lines and an IgM+ B cell line did. The block in XLA B cells was not due to a defect in the basic mechanism of Ca2+ flux generation, as the cells responded well to thapsigargin. In addition, the defect did not affect T cells, which were shown to respond to CD3 antibody with a Ca2+ flux. Ligation of mu heavy chain on XLA bone marrow cells did, however, activate tyrosine kinases, resulting in tyrosine phosphorylation of a cellular protein with a molecular weight of approximately 115 kD. These results indicate that Btk may be necessary for the generation of the Ca2+ flux in response to ligation of mu heavy chain on B cells and mu psiLC+ pre-B.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1998

Improvement of sperm count and motility after ligation of varicoceles detected with colour Doppler ultrasonography.

The debate regarding the efficacy of varicocele ligation for improvement of semen parameters and pregnancy rates is ongoing. In addition, no consensus exists as to the benefit of treatment of subclinical varicoceles. The aim of this study was to investigate, retrospectively, the effect of high ligation of both subclinical and clinical varicoceles on sperm count and motility. The value of several factors from history-taking and physical examination for the prediction of successful varicocelectomy was analysed. A total of 139 patients, operated on for a unilateral varicocele on the left side, were studied. Varicoceles were subclinical in 73 patients, based on colour Doppler ultrasonography, and 66 varicoceles were clinical, based on palpation in addition to ultrasonography. Comparison of semen parameters before and after surgery revealed a significant improvement. The median sperm count increased from 10.0 to 14.7, and from 18.2 to 28.6 million/ejaculate, in patients with subclinical and clinical varicoceles, respectively (p < 0.001). The percentage improvement in median sperm count in subclinical varicoceles was not statistically different from the improvement in clinical varicoceles. Mean progressive motility improved significantly after ligation (p < 0.001). The improvement in motility in subclinical varicoceles, from 16 to 23%, was significantly larger than the 24 to 27% improvement in clinical varicoceles. The increase in sperm count was related positively to testicular volume before surgery (p < 0.05). The increase in sperm motility was significantly lower in patients with a history of cryptorchidism (n = 22, p < 0.05). The present data show that ligation of varicoceles detected using Doppler ultrasonography, whether palpable or not, results in an increase in sperm concentration and motility.

Adult↗
PubMed1999

Does ligation of the hypogastric artery at the time of radical hysterectomy and lymphadenectomy decrease blood loss? Results of a prospective randomized trial.

A prospective, randomized study of patients undergoing radical hysterectomy for gynecologic malignancies was undertaken from 10/95 to 11/96 to determine if ligation of the hypogastric arteries at the time of radical hysterectomy decreases blood loss. Patients were randomized to either ligation of the hypogastric artery (Group 1) or no ligation (Group 2) prior to a standard Piver type III radical hysterectomy. Surgeries were performed by Board certified gynecologic oncologists with gynecologic oncology fellows and/or OB/GYN residents. Patients were analyzed for demographic characteristics and intraoperative and postoperative parameters. Statistical analysis was performed with independent samples t-test, Mann-Whitney rank sum test, Chi square and Fisher exact test. Twenty-one patients were randomized to group 1 and 22 to group 2. Groups were similar with respect to demographics and preoperative parameters except for age. There were no differences among the groups with respect to intraoperative and postoperative parameters. The mean estimated blood loss for group 1 was 600 ml and 550 ml for group 2 (P = NS). Hypogastric artery ligation (HAL) at the time of radical hysterectomy for gynecologic malignancy does not reduce blood loss.

Journal Article↗
PubMed1996

Genotyping of the human platelet antigen systems 1 through 5 by multiplex polymerase chain reaction and ligation-based typing.

BACKGROUND: Platelet-specific antibodies may be involved in refractoriness to platelet transfusions, disorders such as neonatal alloimmune thrombocytopenia, and post-transfusion purpura. Genotyping for the major human platelet antigen (HPA) systems HPA-1 through HPA-5 is of considerable help in establishing the diagnoses of these diseases. STUDY DESIGN AND METHODS: A new genotyping method is described. Alleles of all five systems are amplified in a multiplex polymerase chain reaction. Subsequently, aliquots of the amplification products are thermocycled in the presence of a pair of allele-specific oligonucleotide probes and a heat-stable ligase. After heat denaturation, the probes hybridize adjacent to complementary sequences of the amplification product. In a perfect match, the two probes become covalently joined. Detection of the ligation product is performed with an enzyme-linked immunosorbent assay. RESULTS: Complete concordance of genotypes between the ligation-based typing and established genotyping methods was determined in 54 Austrian (HPA-1, -2, -3, and -5) and 56 Japanese (HPA-4) individuals. Ligation-based genotyping of HPA-1 polymorphism using platelet-derived RNA as starting material gave concordant results in all 15 cases tested. CONCLUSION: Multiplex polymerase chain reaction in combination with ligation-based typing allows fast typing of large numbers of platelet donors and screening for critical antigens in pregnant women.

Base Sequence↗
PubMed1996

Systemic hemodynamics and serum nitrate levels in patients undergoing endoscopic variceal ligation.

The effects of endoscopic variceal ligation (EVL) on systemic hemodynamics are unknown. This study was conducted to determine whether the obliteration of portal-systemic collaterals by EVL affects systemic hemodynamics and serum nitrate concentrations in patients with compensated cirrhosis. We measured systemic and hepatic hemodynamics, azygos vein blood flow (AzBF), and serum nitrate concentrations before and immediately following EVL. A prompt decrease in left ventricular end-diastolic volume (LVEDV), stroke volume, cardiac index (CI), and an increase in systemic vascular resistance index (SVRI) were observed following variceal ligation. The reduction in LVEDV was associated with a decline in CI with a rise in SVRI. There was also a prompt reduction in serum nitrate concentration following variceal ligation. AzBF also significantly decreased following variceal ligation. These findings indicate that EVL decreased cardiac output via a reduction in cardiac preload (central venous return). Blood flow through portal-systemic collaterals has an important role in the enhanced cardiac preload of cirrhotic patients. The sudden decrease in serum nitrate concentrations suggests that endogenous nitric oxide may be involved in the regulation of systemic hemodynamics in patients with compensated cirrhosis.

Aldosterone↗
PubMed2000

Ligation of a patent ductus arteriosus under fentanyl anesthesia improves protein metabolism in premature neonates.

BACKGROUND/PURPOSE: Although surgical ligation effectively reverses the cardiopulmonary failure associated with patent ductus arteriosus (PDA), previous findings have suggested that such surgery itself elicits a catabolic response in premature neonates. Therefore, the authors sought to quantitatively assess whether PDA ligation under fentanyl anesthesia aggravated or improved the protein metabolism of premature neonates. METHODS: Seven ventilated, premature neonates (birth weight 815 +/- 69 g) underwent PDA ligation with standardized fentanyl anesthesia (15 microg/kg) on day-of-life 8.4 +/- 1.2 and were studied immediately pre- and 16 to 24 hours postoperatively while receiving continuous total parenteral nutrition (TPN). Whole-body protein kinetics were calculated using intravenous 1-[13C]leucine, and skeletal muscle protein breakdown was measured from the urinary 3-methylhistidine to creatinine ratio (MH:Cr). RESULTS: Whole-body protein breakdown (10.9 +/- 1.2 v8.9 +/- 0.8 g/kg/d, P < .05), turnover (17.4 +/- 1.2 v 15.4 +/- 0.8 g/kg/d, P< .05), and MH:Cr (1.95 +/- 0.20 v 1.71 +/- 0.16 micromol:mg, P< .05) decreased significantly after operation. This resulted in a 60% improvement in protein balance (1.6 +/- 0.8 v 2.6 +/- 0.6 g/kg/d, P = 0.08) postoperatively. CONCLUSIONS: Because of decreased whole-body protein breakdown, whole-body protein turnover, skeletal muscle protein breakdown, and increased protein accrual, surgical PDA ligation under fentanyl anesthesia promptly improves the protein metabolism of premature neonates enduring the stress of a PDA.

Anesthetics, Intravenous↗
PubMed2001

The effect of lumbar sympathectomy in the spinal nerve ligation model of neuropathic pain.

To evaluate the sympathetic dependency of pain behaviors in an animal model of neuropathic pain, the effect of surgical sympathectomy on the mechanical sensitivity of the hindpaw was examined in rats with L5 spinal nerve ligation. Mechanical sensitivity was determined by measuring foot withdrawal thresholds to mechanical stimulation with von Frey filaments applied to the base of the third or fourth toe. Tight ligation of the segmental L5 spinal nerve led to the development of mechanical hypersensitivity in the hindpaw. The effects of 2 different procedures of surgical lumbar sympathectomy on mechanical hypersensitivity were compared, limited (resection of sympathetic chain/ganglia L2 to L4 segments) and extensive (resection of L2 to L6 segments) sympathectomies. Mechanical hypersensitivity produced by L5 spinal nerve ligation was partially but significantly reduced by both sympathectomy procedures. In a separate group of rats, the L5 spinal nerve was ligated while irritating the neighboring L4 spinal nerve. This procedure produced a lesser degree of mechanical hypersensitivity, and subsequent sympathectomy had no effect on these animals. These data suggest that sympathectomy is effective in this model only when the animals show severe mechanical hypersensitivity.

Journal Article↗
PubMed2002

Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) treated with adenovirus (Ad)-CD154 (CD40L) gene therapy experience reductions in leukemia cell counts and lymph node size associated with induction of the death receptor Fas (CD95). CD4 T cell lines can induce apoptosis of CD40-activated CLL cells via a CD95 ligand (CD95-L)-dependent mechanism. To examine whether CD95-L was sufficient to induce cytolysis of CD40-activated CLL cells, we used Chinese hamster ovary cells transfected with CD95-L as cytotoxic effector cells. CD40-activated CLL cells were initially resistant to CD95-mediated apoptosis despite high-level expression of CD95. However, after 72 h, CLL cells from seven of seven patients became increasingly sensitive to CD95-mediated apoptosis. This sensitivity correlated with a progressive decline in Flice-inhibitory protein (FLIP), which was induced within 24 h of CD40 ligation. Down-regulation of FLIP with an antisense oligonucleotide or a pharmacologic agent, however, was not sufficient to render CLL cells sensitive to CD95-mediated apoptosis in the 24-72 h after CD40 activation. Although the levels of pro-Caspase-8 appeared sufficient, inadequate levels of Fas-associated death domain protein (FADD) and DAP3 may preclude assembly of the death-inducing signaling complex. Seventy-two hours after CD40 ligation, sensitivity to CD95 and a progressive increase in FADD and DAP3 were associated with the acquired ability of FADD and FLIP to coimmunoprecipitate with the death-inducing signaling complex after CD95 ligation. Collectively, these studies reveal that CD40 ligation on CLL B cells induces a programmed series of events in which the cells initially are protected and then sensitized to CD95-mediated apoptosis through shifts in the balance of the anti- and proapoptotic proteins FLIP and FADD.

Animals↗
PubMed2004

Cytokine detection by antibody-based proximity ligation.

Efficient and precise detection techniques, along with extensive repertoires of specific binding reagents, will be needed to meet the challenges of proteome analyses. The recently established proximity ligation mechanism enables sensitive high-capacity protein measurements by converting the detection of specific proteins to the analysis of DNA sequences. Proximity probes containing oligonucleotide extensions are designed to bind pairwise to target proteins and to form amplifiable tag sequences by ligation when brought in proximity. In our previous report, both the ligatable arms and the protein binders were DNA molecules. We now generalize the method by providing simple and convenient protocols to convert any polyclonal antibodies or matched pair of monoclonal antibodies to proximity probe sets through the attachment of oligonucleotide sequences. Sufficient reagent for >100,000 proximity ligation assays can be prepared from 1 microg of antibody. The technique is applied to measure cytokines in a homogenous test format with femtomolar detection sensitivities in 1-microl samples, and we exemplify its utility in situations when only minute sample amounts are available.

Antibodies↗
PubMed1991

RNA-mediated ligation of self-cleavage products of a Neurospora mitochondrial plasmid transcript.

Neurospora VS RNA is a mitochondrial single-stranded RNA that combines certain features of catalytic RNAs and group I introns. We report here that monomeric VS RNA synthesized in vitro by self-cleavage of a multimeric transcript can perform an RNA-mediated self-ligation reaction producing circular RNAs indistinguishable from those isolated from mitochondria. We conclude that the active site for the ligation reaction is present in the RNA itself. Also, the mechanism for aligning the termini to be ligated may be different from mechanisms previously described. The lack of sequence similarity between VS RNA and previously characterized catalytic RNAs suggests that VS RNA is an independently evolved ribozyme capable of both cleavage and ligation.

Base Sequence↗
PubMed1995

CD38 ligation induces tyrosine phosphorylation of Bruton tyrosine kinase and enhanced expression of interleukin 5-receptor alpha chain: synergistic effects with interleukin 5.

Mouse CD38 has been implicated in the regulation of both B-cell proliferation and protection of B cells from irradiation-induced apoptosis. CD38 ligation on B cells by CS/2, an anti-mouse CD38 monoclonal antibody, induced proliferation, IgM secretion, and tyrosine phosphorylation of Bruton tyrosine kinase in B cells from wild-type mice. B cells from X chromosome-linked immunodeficient mice did not respond at all to anti-CD38 antibody, although CD38 expression on these B cells was comparable to that on wild-type B cells. We infer from these results that Bruton tyrosine kinase activation is involved in B-cell triggering after cross-linkage of CD38. Analysis of the synergistic effects of various cytokines with CD38 ligation on B-cell activation revealed that interleukin 5 (IL-5) showed the most potent effect on B-cell proliferation, Blimp1 gene expression, and IgM production. These synergistic effects were not seen with B cells from X chromosome-linked immunodeficient mice. Flow cytometry analysis revealed that CD38 ligation increased surface expression of the IL-5-receptor alpha chain on B cells. These data indicate that CD38 ligation increases IL-5 receptor alpha expression and synergizes with IL-5 to enhance Blimp1 expression and IgM synthesis.

ADP-ribosyl Cyclase↗
PubMed1998

Expressed protein ligation: a general method for protein engineering.

A protein semisynthesis method-expressed protein ligation-is described that involves the chemoselective addition of a peptide to a recombinant protein. This method was used to ligate a phosphotyrosine peptide to the C terminus of the protein tyrosine kinase C-terminal Src kinase (Csk). By intercepting a thioester generated in the recombinant protein with an N-terminal cysteine containing synthetic peptide, near quantitative chemical ligation of the peptide to the protein was achieved. The semisynthetic tail-phosphorylated Csk showed evidence of an intramolecular phosphotyrosine-Src homology 2 interaction and an unexpected increase in catalytic phosphoryl transfer efficiency toward a physiologically relevant substrate compared with the non-tail-phosphorylated control. This work illustrates that expressed protein ligation is a simple and powerful new method in protein engineering to introduce sequences of unnatural amino acids, posttranslational modifications, and biophysical probes into proteins of any size.

Animals↗
PubMed1998

Preparation of functionally active cell-permeable peptides by single-step ligation of two peptide modules.

Noninvasive cellular import of synthetic peptides can be accomplished by incorporating a hydrophobic, membrane-permeable sequence (MPS). Herein, we describe a facile method that expedites synthesis of biologically active, cell-permeable peptides by site-specific ligation of two free peptide modules: one bearing a functional sequence and the second bearing a MPS. A nonpeptide thiazolidino linkage between the two modules is produced by ligation of the COOH-terminal aldehyde on the MPS and the NH2-terminal 1, 2-amino thiol moiety on the functional sequence. This thiazolidine ligation approach is performed with stoichiometric amounts of fully unprotected MPS and functional peptide in an aqueous buffered solution, eliminating the need for additional chemical manipulation and purification prior to use in bioassays. Two different MPSs were interchangeably combined with two different functional sequences to generate two sets of hybrid peptides. One set of hybrid peptides, carrying the cytoplasmic cell adhesion regulatory domain of the human integrin beta3, inhibited adhesion of human erythroleukemia cells to fibrinogen-coated surfaces. A second set of hybrid peptides, carrying the nuclear localization sequence of the transcription factor NF-kappaB, inhibited nuclear import of transcription factors NF-kappaB, activator protein 1, and nuclear factor of activated T cells in agonist-stimulated Jurkat T lymphocytes. In each assay, these nonamide bond hybrids were found to be functionally comparable to peptides prepared by the conventional method. Cumulatively, this new ligation approach provides an easy and rapid method for engineering of functional, cell-permeable peptides and demonstrates the potential for synthesis of cell-permeable peptide libraries designed to block intracellular protein-protein interactions.

Amino Acid Sequence↗
PubMed1999

Ligation of the CD4 receptor induces activation-independent down-regulation of L-selectin.

Lymphocyte circulation plays an important role in the generation of a specific immune response. Mature lymphocytes continuously circulate between blood and lymph, entering the lymphoid tissue via high endothelial venules. Trafficking across high endothelial venules of peripheral lymph nodes (PLN) depends on the expression of L-selectin. It has been shown that L-selectin is rapidly cleaved from the surface by a metalloproteinase after in vitro activation. Here, we show that ligation of CD4, without ligation of the T cell receptor for antigen, causes down-regulation of L-selectin on T helper cells. This down-regulation is caused by proteolytic cleavage by a metalloproteinase and is reversible by the addition of hydroxamic acid-based metalloproteinase inhibitors. We show that in vivo down-regulation of L-selectin in huCD4tg mice by mAb reduces the homing of lymphocytes to PLN in adoptive transfer experiments. Because CD4 is a coreceptor for HIV-1, the down-regulation of L-selectin induced by CD4 ligation could play a role in the pathogenesis of AIDS. We provide evidence that CD4 ligation by HIV-1 induces metalloproteinase-dependent L-selectin down-regulation. Reduced levels of L-selectin expression might contribute to immune deficiency in individuals infected with HIV by inhibiting T cell redistribution and decreasing the probability of an encounter between specific lymphocytes and viral antigens in PLN.

Adoptive Transfer↗
PubMed2000

A host-specific function is required for ligation of a wide variety of ribozyme-processed RNAs.

Hepatitis delta virus (HDV) replicates its circular RNA genome via a rolling circle mechanism. During this process, cis-acting ribozymes cleave adjacent upstream sequences and thereby resolve replication intermediates to unit-length RNA. The subsequent ligation of these 5'OH and 2',3'-cyclic phosphate termini to form circular RNA is an essential step in the life cycle of the virus. Here we present evidence for the involvement of a host activity in the ligation of HDV RNA. We used both HDV and hammerhead ribozymes to generate a panel of HDV and non-HDV RNA substrates that bear 5' hydroxyl and 2', 3'- cyclic phosphate termini. We found that ligation of these substrates occurred in host cells, but not in vitro or in Escherichia coli. The host-specific ligation activity was capable of joining RNA in both bimolecular and intramolecular reactions and functioned in a sequence-independent manner. We conclude that mammalian cells contain a default pathway that efficiently circularizes ribozyme processed RNAs. This pathway could be exploited in the delivery of stable antisense and decoy RNA to the nucleus.

Base Sequence↗
PubMed1999

CTLA-4 ligation suppresses CD28-induced NF-kappaB and AP-1 activity in mouse T cell blasts.

The effects of cytotoxic lymphocyte antigen 4 (CTLA-4) on CD3/CD28 monoclonal antibody (mAb) activation of CD4(+)/CTLA-4(+) blastoid T cells were studied in an in vitro model system. As previously reported, coligation of CTLA-4 mAb results in suppression of T cell proliferation and cytokine production. The proliferation but not the interleukin 2 (IL-2) production could be restored by addition of exogenous IL-2, suggesting that the inhibitory effect occurred at the level of IL-2 production rather than at the regulation of the IL-2 receptor pathway. To study the effects on nuclear factors critical for T cell activation, we analyzed the levels of the transcription factors NF-kappaB and AP-1. These were potently induced in CD3/CD28 mAb-restimulated T cells. In contrast, CTLA-4 ligation strongly suppressed the induction of both transcription factors. The compositions of NF-kappaB and AP-1 family members were similar, irrespective of stimulation conditions. Analyses of the NF-kappaB regulator IkappaB-alpha revealed similar levels of IkappaB-alpha protein in the preparations. However, a reduced phosphorylation of IkappaB-alpha in CTLA-4 coengaged T cell blasts compared with T cells ligated with CD3/CD28 was found. Previous studies have concluded that CTLA-4 ligation regulates T cell activation by inhibiting the T cell receptor-mediated signals. However, the present findings propose that the major impact of CTLA-4 ligation is inhibition of signals mediated by CD28.

Abatacept↗
PubMed1999

Metal-dependent self-assembly of protein tubes from Escherichia coli glutamine synthetase. Cu(2+) EPR studies of the ligation and stoichiometry of intermolecular metal binding sites.

Escherichia coli glutamine synthetase (GS) is a dodecameric assembly of identical subunits arranged as two back-to-back hexagonal rings. In the presence of divalent metal ions, the dodecamers "stack" along their six-fold axis of symmetry to yield elongated tubes. This self-assembly process provides a useful model for probing metal-dependent protein-protein interactions. However, no direct spectroscopic or structural data have confirmed the identity of the ligands to the shared metal ions in "stacked" GS. Here, 9-GHz Cu(2+) EPR studies have been used to probe the ligand structure and stoichiometry of the metal binding sites. The wild type protein, with N-terminal sequence (His-4)-X(3)-(Met-8)-X(3)-(His-12), exhibits a classic Cu(2+)-nitrogen spectrum, with g = 2.06 G, g = 2.24 G, and A = 19.3 x 10(-3) cm(-1). No superhyperfine structure is observed. The H4C mutant affords a spectrum that is the combination of two spectra at all stages of saturation. One of the overlapping spectra is nearly identical to the spectrum of wild type, and is due to His ligation. The second spectrum observed yields g = 2.28 and A = 17.1 x 10(-3) cm(-1). The linewidth and tensor values of the second component have been assigned to Cu(2+)-S ligation. In contrast, the H12C mutant exhibits an EPR spectrum at low Cu(2+) occupancy that is very similar to the second set of spectral features observed for H4C, and which is assigned to Cu(2+)-S ligation. No Cu(2+)-His ligation is apparent until the Cu(2+)/N-terminal helices ratio is >1.0. At saturation, the g = 2.00-2.06 region of the spectrum is essentially a mirror image of the spectrum obtained with H4C, and is due to overlapping Cu(2+)-N and Cu(2+)-S EPR spectra. The M8L and M8C mutants were also studied, in order to probe the role of position 8 in the N-terminal helix. Spectral parameters of these mutants are nearly identical to each other and to the wild type spectrum at saturating Cu(2+), suggesting that Met-8 does not act as a direct metal ligand. Together, the results provide the first direct evidence for a binuclear metal ion site between each N-terminal helix pair at the GS-GS interface, with both His-4 and His-12 providing metal ligands.

Binding Sites↗
PubMed2002

CD27 and CD40 inhibit p53-independent mitochondrial pathways in apoptosis of B cells induced by B cell receptor ligation.

B cells in the germinal center are known to undergo apoptosis after B cell receptor (BCR) ligation, a process relevant to immunological tolerance. Human CD27 is a B cell co-stimulatory molecule. The aim of this study was to compare the effects of CD27 and CD40 signals on BCR-mediated apoptosis of B cells. BCR ligation activated mitochondrial apoptotic pathways including down-regulation of Bcl-X(L), dissipation of mitochondrial transmembrane potential, release of cytochrome c, and activation of caspase-9. Each of these effects was significantly inhibited by CD27 and CD40. Bik expression was weakly but significantly down-regulated by CD27 but up-regulated by CD40. BCR ligation resulted in p53 activation including its phosphorylation at Ser(15), nuclear translocation, and target gene p53AIP1 induction. CD27 and CD40 clearly suppressed these processes. Analyses that used dominant-negative p53 variants revealed a low but still substantial level of BCR-mediated apoptosis and intact mitochondria-mediated apoptotic pathway. These pathways were further inhibited by CD27 and CD40, although the cells showed no p53 phosphorylation or p53AIP1 expression. Our results suggested that, at the mitochondrial level, CD27 and CD40 co-stimulatory signals regulated the p53-amplified apoptotic pathway in B cells through the inhibition of p53-independent apoptotic pathway primarily induced by BCR ligation.

Apoptosis↗