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
2019 ◽  
Author(s):  
Felix Horns ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake

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.


2018 ◽  
pp. 135
Author(s):  
Thomas L. Feldbush ◽  
Laura L. Stunz ◽  
David E. Lafrenz

2019 ◽  
Vol 31 (12) ◽  
pp. 771-779 ◽  
Author(s):  
Sarah Leach ◽  
Ryo Shinnakasu ◽  
Yu Adachi ◽  
Masatoshi Momota ◽  
Chieko Makino-Okamura ◽  
...  

Memory B cells protect against heterologous influenza infection


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 ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Emmanuelle Dugas-Bourdages ◽  
Sonia Néron ◽  
Annie Roy ◽  
André Darveau ◽  
Robert Delage

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.


2015 ◽  
Vol 195 (12) ◽  
pp. 5592-5601 ◽  
Author(s):  
Sofia Järnum ◽  
Robert Bockermann ◽  
Anna Runström ◽  
Lena Winstedt ◽  
Christian Kjellman

2021 ◽  
Author(s):  
Nida Meednu ◽  
Javier Rangel-Moreno ◽  
Fan Zhang ◽  
Katherine Escalera-Rivera ◽  
Elisa Corsiero ◽  
...  

Ectopic lymphoid structures (ELS) are present in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and the role of in situ synovial B cell differentiation and selection in disease are not well understood. Here, we identified a B cell population in the synovium characterized by expression of NR4A1-3, a family of orphan nuclear receptors, that is highly enriched at both early and late stages of RA. NR4A B cells are rare in healthy peripheral blood, RA blood, and SLE kidney, but share markers with blood transcriptomic signatures that peak during RA disease flare. Using combined single cell transcriptomics and B cell receptor (BCR) sequencing, we demonstrate that NR4A synovial B cells have an activated transcriptomic profile that significantly overlaps with germinal center (GC) light zone (LZ) B cells and an accrual of somatic hypermutation that correlates with loss of naive B cell status. NR4A B cells uniquely co-express lymphotoxin β and IL6, supporting important functions in ELS promotion and pro-inflammatory cytokine production. The presence of shared clones in this activated B cell state, NR4A expressing synovial plasma cells (PC), and CCR6+ memory B cell (MBC) precursors further points to in situ differentiation. NR4A1 was expressed at the protein level in RA synovial B cells and PC, was high in tonsil GC B cells with a LZ-DZ intermediate phenotype, and was rapidly induced at both the RNA and protein level upon activation through the BCR. Taken together, we identified a dynamic progression of B cell activation in RA synovial ELS, with NR4A as a read-out of likely antigen activation and local adaptive immune responses.


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