scholarly journals Transcriptional program of memory B cell activation, broadly binding anti-influenza antibodies, and bystander activation after vaccination revealed by single-cell transcriptomics

2019 ◽  
Author(s):  
Felix Horns ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake
Keyword(s):  
Influenza Vaccination ◽  
B Cell ◽  
Single Cell ◽  
Cell Activation ◽  
Transcriptional Profiling ◽  
Affinity Maturation ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Memory B Cell ◽  
Clonal Proliferation

AbstractAntibody memory protects humans from many diseases. Protective antibody memory responses require activation of transcriptional programs, cell proliferation, and production of antigen-specific antibodies, but how these aspects of the response are coordinated is poorly understood. We profiled the molecular and cellular features of the antibody response to influenza vaccination by integrating single-cell transcriptomics, longitudinal antibody repertoire sequencing, and antibody binding measurements. Single-cell transcriptional profiling revealed a program of memory B cell activation characterized by CD11c and T-bet expression associated with clonal expansion and differentiation toward effector function. Vaccination elicited an antibody clone which rapidly acquired broad high-affinity hemagglutinin binding during affinity maturation. Unexpectedly, many antibody clones elicited by vaccination do not bind vaccine, demonstrating non-specific activation of bystander antibodies by influenza vaccination. These results offer insight into how molecular recognition, transcriptional programs, and clonal proliferation are coordinated in the human B cell repertoire during memory recall.

scholarly journals Memory B Cell Activation, Broad Anti-influenza Antibodies, and Bystander Activation Revealed by Single-Cell Transcriptomics

Cell Reports ◽  
2020 ◽  
Vol 30 (3) ◽  
pp. 905-913.e6 ◽  
Author(s):  
Felix Horns ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake
Keyword(s):  
B Cell ◽  
Single Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Memory B Cell ◽  
Bystander Activation

Memory B Cell Activation, Differentiation, and Isotype Switching

2018 ◽  
pp. 135
Author(s):  
Thomas L. Feldbush ◽  
Laura L. Stunz ◽  
David E. Lafrenz
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Isotype Switching ◽  
Memory B Cell

scholarly journals Requirement for memory B-cell activation in protection from heterologous influenza virus reinfection

2019 ◽  
Vol 31 (12) ◽  
pp. 771-779 ◽  
Author(s):  
Sarah Leach ◽  
Ryo Shinnakasu ◽  
Yu Adachi ◽  
Masatoshi Momota ◽  
Chieko Makino-Okamura ◽  
...  
Keyword(s):  
Influenza Virus ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Influenza Infection ◽  
Memory B Cells ◽  
B Cell Activation ◽  
Memory B Cell

Memory B cells protect against heterologous influenza infection

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.

scholarly journals Intrathecal B-cell activation in LGI1 antibody encephalitis

2020 ◽  
Vol 7 (2) ◽  
pp. e669 ◽  
Author(s):  
Klaus Lehmann-Horn ◽  
Sarosh R. Irani ◽  
Shengzhi Wang ◽  
Arumugam Palanichamy ◽  
Sarah Jahn ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Cell Activity ◽  
Oligoclonal Bands ◽  
B Cell Activation ◽  
Cell Repertoire ◽  
Antibody Titers ◽  
B Cell Subsets

ObjectiveTo study intrathecal B-cell activity in leucine-rich, glioma-inactivated 1 (LGI1) antibody encephalitis. In patients with LGI1 antibodies, the lack of CSF lymphocytosis or oligoclonal bands and serum-predominant LGI1 antibodies suggests a peripherally initiated immune response. However, it is unknown whether B cells within the CNS contribute to the ongoing pathogenesis of LGI1 antibody encephalitis.MethodsPaired CSF and peripheral blood (PB) mononuclear cells were collected from 6 patients with LGI1 antibody encephalitis and 2 patients with other neurologic diseases. Deep B-cell immune repertoire sequencing was performed on immunoglobulin heavy chain transcripts from CSF B cells and sorted PB B-cell subsets. In addition, LGI1 antibody levels were determined in CSF and PB.ResultsSerum LGI1 antibody titers were on average 127-fold higher than CSF LGI1 antibody titers. Yet, deep B-cell repertoire analysis demonstrated a restricted CSF repertoire with frequent extensive clusters of clonally related B cells connected to mature PB B cells. These clusters showed intensive mutational activity of CSF B cells, providing strong evidence for an independent CNS-based antigen-driven response in patients with LGI1 antibody encephalitis but not in controls.ConclusionsOur results demonstrate that intrathecal immunoglobulin repertoire expansion is a feature of LGI1 antibody encephalitis and suggests a need for CNS-penetrant therapies.

scholarly journals Chronic signs of memory B cell activation in patients with Behçet’s disease are partially restored by anti-tumour necrosis factor treatment

Rheumatology ◽  
2016 ◽  
Vol 56 (1) ◽  
pp. 134-144 ◽  
Author(s):  
Tim B. van der Houwen ◽  
P. Martin van Hagen ◽  
Wilhemina M. C. Timmermans ◽  
Sophinus J. W. Bartol ◽  
King H. Lam ◽  
...  
Keyword(s):  
B Cell ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Cell Activation ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
B Cell Activation ◽  
Memory B Cell ◽  
Behcet's Disease ◽  
Necrosis Factor

scholarly journals Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Emmanuelle Dugas-Bourdages ◽  
Sonia Néron ◽  
Annie Roy ◽  
André Darveau ◽  
Robert Delage
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Memory B Cell ◽  
Activation Pathway ◽  
Culture Model ◽  
Normal Controls ◽  
Binucleated Lymphocytes

Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion within vitroisotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway.

Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis

2018 ◽  
Vol 78 (2) ◽  
pp. 282-284
Author(s):  
Jin Kyun Park ◽  
Ye Ji Lee ◽  
Samuel Bitoun ◽  
Kevin L Winthrop ◽  
Yunhee Choi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Influenza Vaccination ◽  
B Cell ◽  
Cell Activation ◽  
Seasonal Influenza ◽  
B Cell Activation ◽  
Seasonal Influenza Vaccination ◽  
Activation Factor

scholarly journals Systemic autoimmune disease arises from polyclonal B cell activation.

1987 ◽  
Vol 165 (6) ◽  
pp. 1755-1760 ◽  
Author(s):  
D M Klinman ◽  
A D Steinberg
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Systemic Autoimmune Disease ◽  
Single Cell Level ◽  
B Cell Activation ◽  
Cell Level ◽  
Cell Repertoire ◽  
Systemic Autoimmune Diseases ◽  
B Cell Repertoire

The number of B cells producing antibodies reactive with any of seven autoantigens or two conventional antigens was compared at the single-cell level to the total number of Ig-secreting B cells present in the spleens of NZB, MRL lpr/lpr, and BXSB autoimmune mice. The proportion of lymphocytes producing antibodies of each specificity, expressed as a percentage of the total B cell repertoire, was virtually identical among autoimmune and congenic nonautoimmune animals. Furthermore, B cells and serum antibodies reactive with conventional antigens increased commensurately with those reactive with autoantigens. These results indicate that systemic autoimmune diseases arise from polyclonal B cell activation.

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