A5080463871- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Blood groups and transfusion
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- RNA Research and Splicing
- Galectins and Cancer Biology
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Reproductive System and Pregnancy
- Complement system in diseases
- Immunodeficiency and Autoimmune Disorders
- Nuclear Structure and Function
- Cell death mechanisms and regulation
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Transplantation: Methods and Outcomes
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
Sanofi (United States)
2022-2025
US Biologic (United States)
2021
John Wiley & Sons (Germany)
2018
University of Pennsylvania
1997-2012
Biogen (United States)
2003-2011
National Institutes of Health
2011
National Heart Lung and Blood Institute
2011
Thomas Jefferson University
2002
Sidney Kimmel Cancer Center
2001
Virginia Mason Medical Center
1996
Abstract The TNF-related ligand, B cell-activating factor belonging to the TNF family (BAFF), is necessary for normal cell development and survival, specifically binds receptors transmembrane activator calcium-modulator cyclophilin ligand interactor (TACI), maturation Ag (BCMA), BAFF-R. Similarities between mice completely lacking BAFF A/WySnJ strain that express a naturally occurring mutant form of BAFF-R suggest acts primarily through However, nearly full-length protein expressed by makes...
The factors regulating germinal center (GC) B cell fate are poorly understood. Recent studies have defined a crucial role for the cell–activating factor belonging to TNF family (BAFF; also called BLyS) in promoting primary survival and development. A this cytokine antigen-driven responses has been suggested but current data regard limited. BAFF receptor expressed by cells (BAFF-R/BR3) is defective A/WySnJ mice which exhibit phenotype similar BAFF-deficient (BAFF−/−) animals. Here, we show...
Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and effective in depleting lymphocytes by cytolytic effects vivo. Although the of alemtuzumab are dependent on density antigen cells, there scant information regarding expression levels different types. In this study, was assessed phenotypically distinct subsets lymphoid myeloid cells peripheral blood mononuclear (PBMCs) from normal donors. Results demonstrate PBMCs express differing CD52. Quantitative analysis showed memory...
Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, were thought to recombine only in forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us question whether these symmetrical might enable bidirectional...
Abstract Germinal centers (GCs) form in B cell follicles and require specific signals for development maintenance. cell-activating factor belonging to the TNF family (BAFF) is a fundamental survival therefore may influence GC reactions subsequent Ab responses. To test this possibility, effect of BAFF neutralization immunized mice was assessed. Using maturation Ag-Fc, we demonstrate that blockade does not inhibit formation or somatic hypermutation. However, GCs Ag-Fc-treated dissipated more...
The expressed human Ig repertoire is not an equal representation of all V(H) segments present in genomic DNA. Studies have shown that a restricted set gene are over-represented Ab repertoires fetal/neonatal and adult B cells. Additionally, this genes frequently by autoimmune tumor To investigate at which developmental stage bias the begins, we compared V(H)3 V(H)4 family pre-B immature cells from bone marrow mature peripheral blood two adults. We found V4-34 V4-59 V3-23 segment dominate...
The TAPR locus containing the TIM gene family is implicated in development of atopic inflammation mouse, and TIM-1 allelic variation has been associated with incidence atopy human patient populations. In this study, we show that manipulation pathway influences airway pathology. Anti-TIM-1 mAbs recognizing distinct epitopes differentially modulated OVA-induced lung mouse. recognized by these Abs were mapped, revealing to both IgV stalk domains have therapeutic activity. Unexpectedly, unique...
Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate survival, cell cycle progression, trafficking resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for development novel molecular targeted therapies. We observed that primary B-cell precursors aberrantly express receptors BAFF-system, BAFF-R,...
Certain VH genes are predominantly expressed in mature B cells. We hypothesized that several, mutually nonexclusive VH-dependent mechanisms operating at distinct stages during cell development may be responsible for overrepresentation of these genes. In the present study, we have assessed whether one involves preferential rearrangement pro-B stage. The frequency individual VH4 and VH3 libraries from FACS-purified human CD34+/CD19+ CD34-/CD19+ pre-B cells was assessed. in-frame out-of-frame...
Abstract The murine low-affinity receptor for IgG, FcγRIIB, mediates inhibition of B cell receptor-triggered events in primary cells. We investigated the expression FcγRIIB on germinal center (GC) cells to better understand its role memory development. Immunohistological analyses demonstrated differential regulation GC Its levels are markedly down-regulated and up-regulated follicular dendritic (FDC) at all times during response. Analyses surface by flow cytometry mRNA RT-PCR analysis...
Molecular characterization of antibody immunity and human discovery is mainly carried out using peripheral memory B cells, occasionally plasmablasts, that express cell receptors (BCRs) on their surface. Despite the importance plasma cells (PCs) as dominant source circulating antibodies in serum, PCs are rarely utilized because they do not surface BCRs cannot be analyzed antigen-based fluorescence-activated sorting. Here, we studied encoded by entire mature populations, including PCs,...
Hybridoma technology has been valuable in the development of therapeutic antibodies. More recently, antigen-specific B-cell selection and display technologies are also gaining importance. A major limitation these approaches used for antibody discovery is extensive process cloning expression involved transitioning from identification to validating function, which compromises throughput discovery. In this study, we describe a identify rapidly re-format express antibodies functional...
Abstract Immunization based antibody discovery is plagued by the paucity of antigen-specific B cells. Identifying these cells akin to finding needle in a haystack. Current and emerging technologies while effective, are limited terms capturing repertoire. We report on bulk purification B-cells benefits it offers various platforms. Using five different antigens, we show hit rates 51–88%, compared about 5% with conventional methods. also that this highly efficient loss only 2% antigen specific...
Animal-derived antibody sources, particularly, transgenic mice that are engineered with human immunoglobulin loci, along advanced generation technology platforms have facilitated the discoveries of therapeutics. For example, isolation antigen-specific B cells, microfluidics, and next-generation sequencing emerged as powerful tools for identifying developing monoclonal antibodies (mAbs). These technologies enable not only drug discovery but also lead to understanding cell biology, immune...
Abstract The acquisition of somatic mutations in the rearranged immunoglobulin V regions B cells occurs within tightly regulated microenvironment a germinal centre. precise mechanism responsible for turning on mutational process is unknown. To dissect role different components centre this mechanism, we have used vitro cultures normal human IgD+ peripheral blood lymphocytes co-cultured with activated CD4+ T cells, or resting CD40 ligand and IL-4. We observed that if included then up to 100%...
Abstract Antibodies, fundamental to immune defense, derive their diversity primarily from the intricate rearrangement of variable (V), (D), and joining (J) gene segments. Traditionally, D genes in forward (5’-3’) direction contribute this by rearranging with V J However, existence significance inverted (InvDs), which are oriented (3’-5’) direction, were previously obscured limitations data detection methods. Here, we carried out a comprehensive analysis large-scale public next-generation...
Expression of the protooncogene A-myb is restricted to developing CNS, adult testes, breasts in late pregnancy, and germinal centers secondary B cell follicles. The functional relevance expression at three these sites has been demonstrated previously via generation analysis A-myb-deficient mice, which display behavioral abnormalities, male sterility, perturbed breast development during pregnancy. In contrast, here we show that center response driven by T cell-dependent Ag immunization...