scholarly journals Distinct B cell subsets give rise to antigen-specific antibody responses against SARS-CoV-2

2020 ◽  
Author(s):  
Patrick Wilson ◽  
Christopher Stamper ◽  
Haley Dugan ◽  
Lei Li ◽  
Nicholas Asby ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Affinity Maturation ◽  
Symptom Duration ◽  
Reading Frame ◽  
Sequencing Platform ◽  
Immune Correlates ◽  
Cell Immunity ◽  
B Cell Subsets ◽  
Human B Cell

Abstract Discovery of durable memory B cell (MBC) subsets against neutralizing viral epitopes is critical for determining immune correlates of protection from SARS-CoV-2 infection. Here, we identified functionally distinct SARS-CoV-2-reactive B cell subsets by profiling the repertoire of convalescent COVID-19 patients using a high-throughput B cell sorting and sequencing platform. Utilizing barcoded SARS-CoV-2 antigen baits, we isolated thousands of B cells that segregated into discrete functional subsets specific for the spike, nucleocapsid protein (NP), and open reading frame (ORF) proteins 7a and 8. Spike-specific B cells were enriched in canonical MBC clusters, and monoclonal antibodies (mAbs) from these cells were potently neutralizing. By contrast, B cells specific to ORF8 and NP were enriched in naïve and innate-like clusters, and mAbs against these targets were exclusively non-neutralizing. Finally, we identified that B cell specificity, subset distribution, and affinity maturation were impacted by clinical features such as age, sex, and symptom duration. Together, our data provide a comprehensive tool for evaluating B cell immunity to SARS-CoV-2 infection or vaccination and highlight the complexity of the human B cell response to SARS-CoV-2.

scholarly journals Specific In Vivo Deletion of B-Cell Subpopulations Expressing Human Immunoglobulins by the B-Cell Superantigen Protein L

2004 ◽  
Vol 72 (6) ◽  
pp. 3515-3523 ◽  
Author(s):  
Muriel Viau ◽  
Nancy S. Longo ◽  
Peter E. Lipsky ◽  
Lars Björck ◽  
Moncef Zouali
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immune Defense ◽  
Protein L ◽  
Variable Regions ◽  
Marginal Zone B Cells ◽  
Human Immunoglobulins ◽  
Cell Immunity ◽  
B Cell Subsets

ABSTRACT Some pathogens have evolved to produce proteins, called B-cell superantigens, that can interact with human immunoglobulin variable regions, independently of the combining site, and activate B lymphocytes that express the target immunoglobulins. However, the in vivo consequences of these interactions on human B-cell numbers and function are largely unknown. Using transgenic mice expressing fully human immunoglobulins, we studied the consequences of in vivo exposure of protein L of Peptostreptococcus magnus with human immunoglobulins. In the mature pool of B cells, protein L exposure resulted in a specific reduction of splenic marginal-zone B cells and peritoneal B-1 cells. Splenic B cells exhibited a skewed light-chain repertoire consistent with the capacity of protein L to bind specific kappa gene products. Remarkably, these two B-cell subsets are implicated in innate B-cell immunity, allowing rapid clearance of pathogens. Thus, the present study reveals a novel mechanism that may be used by some infectious agents to subvert a first line of the host's immune defense.

scholarly journals The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

2021 ◽  
Vol 118 (24) ◽  
pp. e2024624118
Author(s):  
Sarah Pyfrom ◽  
Bam Paneru ◽  
James J. Knox ◽  
Michael P. Cancro ◽  
Sylvia Posso ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
X Chromosome ◽  
Epigenetic Regulation ◽  
Healthy Human ◽  
Linked Gene ◽  
Xist Rna ◽  
B Cell Subsets ◽  
Human B Cell

Systemic lupus erythematous (SLE) is a female-predominant disease characterized by autoimmune B cells and pathogenic autoantibody production. Individuals with two or more X chromosomes are at increased risk for SLE, suggesting that X-linked genes contribute to the observed sex bias of this disease. To normalize X-linked gene expression between sexes, one X in female cells is randomly selected for transcriptional silencing through X-chromosome inactivation (XCI), resulting in allele-specific enrichment of epigenetic modifications, including histone methylation and the long noncoding RNA XIST/Xist on the inactive X (Xi). As we have previously shown that epigenetic regulation of the Xi in female lymphocytes from mice is unexpectedly dynamic, we used RNA fluorescence in situ hybridization and immunofluorescence to profile epigenetic features of the Xi at the single-cell level in human B cell subsets from pediatric and adult SLE patients and healthy controls. Our data reveal that abnormal XCI maintenance in B cells is a feature of SLE. Using single-cell and bulk-cell RNA sequencing datasets, we found that X-linked immunity genes escape XCI in specific healthy human B cell subsets and that human SLE B cells exhibit aberrant expression of X-linked genes and XIST RNA interactome genes. Our data reveal that mislocalized XIST RNA, coupled with a dramatic reduction in heterochromatic modifications at the Xi in SLE, predispose for aberrant X-linked gene expression from the Xi, thus defining a genetic and epigenetic pathway that affects X-linked gene expression in human SLE B cells and likely contributes to the female bias in SLE.

scholarly journals Humoral immunity in atherosclerosis and myocardial infarction: from B cells to antibodies

2021 ◽  
Author(s):  
Florentina Porsch ◽  
Ziad Mallat ◽  
Christoph J Binder
Keyword(s):  
Cardiovascular Disease ◽  
B Cells ◽  
B Cell ◽  
Humoral Immunity ◽  
Clinical Manifestations ◽  
Vascular Wall ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cell Functions ◽  
Cell Immunity ◽  
B Cell Subsets

Abstract Immune mechanisms are critically involved in the pathogenesis of atherosclerosis and its clinical manifestations. Associations of specific antibody levels and defined B cell subsets with cardiovascular disease activity in humans as well as mounting evidence from preclinical models demonstrate a role of B cells and humoral immunity in atherosclerotic cardiovascular disease. These include all aspects of B cell immunity, the generation of antigen-specific antibodies, antigen presentation and co-stimulation of T cells, as well as production of cytokines. Through their impact on adaptive and innate immune responses and the regulation of many other immune cells, B cells mediate both protective and detrimental effects in cardiovascular disease. Several antigens derived from (oxidised) lipoproteins, the vascular wall and classical autoantigens have been identified. The unique antibody responses they trigger and their relationship with atherosclerotic cardiovascular disease are reviewed. In particular, we focus on the different effector functions of specific IgM, IgG, and IgE antibodies and the cellular responses they trigger and highlight potential strategies to target B cell functions for therapy.

scholarly journals The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients

2020 ◽  
Author(s):  
Sarah Pyfrom ◽  
Bam Paneru ◽  
James J. Knoxx ◽  
Michael P. Cancro ◽  
Sylvia Posso ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
X Chromosome ◽  
Epigenetic Regulation ◽  
Healthy Human ◽  
Linked Gene ◽  
Xist Rna ◽  
B Cell Subsets ◽  
Human B Cell

ABSTRACTSystemic lupus erythematous (SLE) is a female-predominant disease characterized by autoimmune B cells and pathogenic autoantibody production. Individuals with two or more X chromosomes are at increased risk for SLE, suggesting that X-linked genes contribute to the observed sex-bias of this disease. To normalize X-linked gene expression between sexes, one X in female cells is randomly selected for transcriptional silencing through X-Chromosome Inactivation (XCI), resulting in allele-specific enrichment of epigenetic modifications, including histone methylation and the long noncoding RNA XIST/Xist on the inactive X (Xi). As we have previously shown that epigenetic regulation of the Xi in female lymphocytes from mice is unexpectedly dynamic, we used RNA FISH and immunofluorescence to profile epigenetic features of the Xi at the single cell level in human B cell subsets from pediatric and adult SLE patients and healthy controls. Our data reveal that abnormal XCI maintenance in B cells is a feature of SLE. Using single-cell and bulk cell RNA sequencing datasets, we found that novel X-linked immunity genes escape XCI in specific healthy human B cell subsets, and that human SLE B cells exhibit aberrant expression of X-linked genes and XIST RNA Interactome genes. Our data reveal that mislocalized XIST RNA, coupled with a dramatic reduction in heterochromatic modifications at the Xi in SLE, predispose for aberrant X-linked gene expression from the Xi, thus defining a novel genetic and epigenetic pathway that affects X-linked gene expression in human SLE B cells and likely contributes to the female-bias in SLE.

TCL1 Expression in B-Cell Tumors Is Dynamically Regulated by Maturation Stage, Proliferation, and the Follicular Microenvironment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4333-4333
Author(s):  
Marco Herling ◽  
Ryuji Kobayashi ◽  
Kaushali A. Patel ◽  
Kong Chao Chang ◽  
Ellen Schlette ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Tumor Cells ◽  
Germinal Center ◽  
Cell Lymphoma ◽  
Maturation Stage ◽  
Dynamic Regulation ◽  
B Cell Subsets ◽  
Human B Cell

Abstract The kinase comodulator TCL1 is the primary initiating oncogene in T-cell prolymphocytic leukemia and can produce B-cell or T-cell chronic lymphocytic leukemia (CLL) following transgenic expression in mice. Given its strong expression in some non-neoplastic B-cell subsets, the role of TCL1 as an oncogene in human B-cell tumors is less clear. Using a recently developed TCL1 monoclonal antibody (clone 1–21), we examined the relationship between TCL1 expression and B-cell maturation stage in tumor tissue arrays, lymphoma cell lines, primary tumor samples and in vitro stimulation assays. Results were compared with immunohistochemical expression of a variety of maturation, activation and cell proliferation markers and with the somatic hypermutation status determined by VH transcript analysis (<2% sequence divergence in VH regarded as “pre-germinal center”). In non-neoplastic B-cells, TCL1 was strongly and uniformly expressed in naive B-cell subsets, but was variably expressed in subsets of germinal center B-cells, with complete absence of expression in immunoblasts and plasma cells. In germinal center B-cells, TCL1 was expressed more strongly in the quiescent centrocyte fraction than in the proliferating centroblasts. This pattern was replicated in human B-cell lymphoma lines and tumors with complete absence of TCL1 in myeloma cases (n = 35) and monocytoid B-cells in marginal zone lymphoma (n = 8) and dim or absent expression in the majority of the mutated/post-germinal center subset of B-CLL (10/15, 67%). In contrast, TCL1 showed strong but modulated expression in the majority of unmutated/pre-germinal center type of B-CLL (14/19, 74%), and mantle cell lymphoma (MCL, 44/57, 84%), and less frequently in follicular lymphoma (FL, 21/47, 45%). In B-CLL, TCL1 was overexpressed in non-proliferating cells within the pseudo-follicular proliferation centers but was markedly downregulated in the CD23+bright PCNA+ proliferating tumor cell component. Similarly in MCL, TCL1 was downregulated in the proliferative component but upregulated in tumor cells in follicular and mantle zone locations versus the diffuse areas. In FL, the highest levels of TCL1 expression were found in those cases that most strongly expressed the germinal center markers CD10 and bcl-6, but TCL1 staining was inversely correlated with expression of proliferation and activation markers, such as CD23. In 3 FL cases with multiple biopsies at different tissue sites, TCL1 was downregulated in tumor cells at extranodal sites as compared to those within lymph node follicles. Thus, the dynamic regulation of TCL1 in B-cells and derived tumors is likely due to changes in the balance between stimulatory microenvironmental influences within the lymphoid follicle and inhibitory signals during cell cycle progression/proliferation. In post-germinal center tumors, TCL1 expression is effectively silenced, and no longer exhibits this dynamic regulation pattern. These studies strongly suggest that TCL1 exerts its effects in promoting cell survival in quiescent B-cell subsets prior to and in the absence of an (antigenic) proliferative signal.

The CD21low B Cell Population Is Composed of an Anergic and an Immunostimulatory Germinal Center-like B Cell Subset

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1425-1425
Author(s):  
Alexander Shimabukuro-Vornhagen ◽  
María García Márquez ◽  
Rieke Fischer ◽  
Kerstin Wennhold ◽  
Juliane Iltgen ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Functional State ◽  
Cell Subset ◽  
Cell Compartment ◽  
Inflammatory Conditions ◽  
Cell Subpopulations ◽  
B Cell Subsets ◽  
Antigen Presenting ◽  
Human B Cell

Abstract In recent years we have gained an increased understanding of the complexity of B cell biology and function. It has become increasingly recognized that apart from antibody production B cells exert many more function. B cells serve as antigen-presenting cells (APC), they contribute to immunoregulation and represent an important source of cytokines and chemokines. A deeper understanding of the role of B cells in the pathophysiology of human diseases has been hampered by the lack of well-defined functional B cell subsets. We therefore aimed to identify novel human B cell subsets which could serve as biomarkers or targets of therapeutic intervention. Using a transcriptomic approach combined with flowcytometric immune assessment of healthy human subjects and patients we were able to identify several functional B cell subpopulations with relevance to human disease. We were able to define a CD21low CD86pos human B cell subset with strong antigen-presenting capacity which gradually develops from conventional resting B cells under the continuous stimulation via CD40. These cells were phenotypically and functionally distinct from CD21low CD86neg B lymphocytes, which represent anergic B cells. Using calcium flux assays and phospho-specific flow cytometry we were able to show that the CD21low B cell subsets displayed distinct signaling states. Both CD21low B cell subpopulations had an impaired response to B cell receptor stimulation. However, CD21low CD86pos B cells had higher basal calcium levels and basal phosphorylation of BCR-associated signaling molecules such as Syk and Erk. Contrary to CD21low CD86neg B cells, which demonstrated poor antigen-presenting capacity, CD21low CD86pos B cells were potent immunostimulatory antigen-presenting cells. CD21low CD86pos B cells were increased in acute inflammation and autoimmune diseases such as rheumatoid arthritis. CD21low CD86neg B cells, on the other hand, were increased in chronic inflammatory conditions such as chronic HIV infection. The balance between the CD21low B cell subsets varied with the functional state of the B cell compartment in inflammatory conditions and could be used to classify the functional state of the B cell compartment. In summary, we have identified several novel human B cell subsets with distinct functions. Given the large number of B cell-directed drugs which are in clinical development or already approved it seems likely that an increased knowledge of the human B cell subsets will not only provide important insights into the pathology of immune-mediated diseases but will also result in novel therapeutic strategies. Disclosures No relevant conflicts of interest to declare.

scholarly journals Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation

2020 ◽  
Author(s):  
Hamish W King ◽  
Nara Orban ◽  
John C Riches ◽  
Andrew J Clear ◽  
Gary Warnes ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Affinity Maturation ◽  
Germinal Centre ◽  
Integrated Analysis ◽  
Cell Mediated Immunity ◽  
Antibody Repertoires ◽  
B Cell Subsets

AbstractIn response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states and their antibody-based selection is challenging to decipher in primary human tissue. We have applied an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics of human B cells undergoing affinity maturation. We define unique gene expression and antibody repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo class switch recombination. We dissect antibody class-dependent gene expression of germinal centre and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B cells to undergo antibody-based selection and differentiate. Together, our analyses provide unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated immunity.

Lymphoproliferative disorders (LPD) involving lungs: T and B cell subsets within pulmonary infiltrates and in peripheral blood

1984 ◽  
Vol 42 ◽  
pp. 700-701
Author(s):  
Irene Stachura ◽  
Milton H. Dalbow ◽  
Michael J. Niemiec ◽  
Matias Pardo ◽  
Gurmukh Singh ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Lymphoproliferative Disorders ◽  
Mixed Population ◽  
Lymphoid Cells ◽  
Lymphomatoid Granulomatosis ◽  
Cell Type ◽  
Cell Surface Antigens ◽  
Pulmonary Infiltrates ◽  
B Cell Subsets

Lymphoid cells were analyzed within pulmonary infiltrates of six patients with lymphoproliferative disorders involving lungs by immunofluorescence and immunoperoxidase techniques utilizing monoclonal antibodies to cell surface antigens T11 (total T), T4 (inducer/helper T), T8 (cytotoxic/suppressor T) and B1 (B cells) and the antisera against heavy (G,A,M) and light (kappa, lambda) immunoglobulin chains. Three patients had pseudolymphoma, two patients had lymphoma and one patient had lymphomatoid granulomatosis.A mixed population of cells was present in tissue infiltrates from the three patients with pseudolymphoma, IgM-kappa producing cells constituted the main B cell type in one patient. In two patients with lymphoma pattern the infiltrates were composed exclusively of T4+ cells and IgG-lambda B cells predominated slightly in the patient with lymphomatoid granulomatosis.

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals Hyper‐metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniela Frasca ◽  
Maria Romero ◽  
Denisse Garcia ◽  
Alain Diaz ◽  
Bonnie B. Blomberg
Keyword(s):  
B Cells ◽  
B Cell ◽  
Inflammatory Markers ◽  
Cell Subset ◽  
Antibody Responses ◽  
Metabolic Phenotype ◽  
Cellular Mechanisms ◽  
Autoimmune Antibodies ◽  
B Cell Subsets ◽  
Old Mice

Abstract Background Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. Methods Splenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer. Results Results have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion. Conclusions These results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.

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