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Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus
Autoantibody production is a hallmark of systemic lupus erythematosus (SLE). Here, the authors demonstrate that antibody-secreting cells from patients with SLE display features of premature maturation and increased survival, which are mediated by intrinsic and extrinsic programmes including autocrine APRIL.
- Weirong Chen
- , So-Hee Hong
- & Ignacio Sanz
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| Open Access
SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells
Linking proteins secreted from individual cells with other cellular information is challenging. Here, authors report a high-throughput method which uses hydrogel nanovials loaded with single cells to link the secretion profile of individual cells with their surface markers and transcriptomic data.
- Rene Yu-Hong Cheng
- , Joseph de Rutte
- & Richard G. James
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| Open Access
Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells
The dysfunction of IL-10 secreting regulatory B cells has been linked to the pathogenesis of autoimmune disease. Here the authors show that low dose IL-2 therapy can enhance IL-10 production in regulatory B cell populations via the modulation of BACH2.
- Akimichi Inaba
- , Zewen Kelvin Tuong
- & Menna R. Clatworthy
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| Open Access
B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation
Class switch recombination (CSR) is a process by which B cells switch their immunoglobulin isotype and develop pathogen-eliminating antibodies. Here, the authors show that a protein kinase DYRK1A is required for protection from viral infection through the regulation of CSR and effective clonal expansion.
- Liat Stoler-Barak
- , Ethan Harris
- & Ziv Shulman
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Article
| Open Access
A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation
Plasma cells are terminally differentiated B cells that are specialized for antibody secretion. Authors show here that genomic deletion of the p38α mitogen activated protein kinase specifically in the B cell lineage leads to diminished plasma cell differentiation via impairment of a transcriptional regulatory program by BLIMP1.
- Jianfeng Wu
- , Kang Yang
- & Jiahuai Han
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Article
| Open Access
Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo
Plasma B cells (PC) are a potential source for protein replacement as they could be engineered to secrete protein other than antibody. Here the authors engineer B cells to express exogenous proteins and demonstrate that these cells can persist long term in adoptive transfer experiments in mice.
- Rene Yu-Hong Cheng
- , King L. Hung
- & Richard G. James
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Article
| Open Access
The phosphatase PTEN links platelets with immune regulatory functions of mouse T follicular helper cells
Platelets have been shown to alter immune cell function but it is not clear if this includes autoimmunity. Here the authors show that phosphatase and tensin homolog (PTEN) deficient platelets promote autoimmunity in mouse models through excessive activation of TFH cells and systemic autoimmune pathology.
- Xue Chen
- , Yanyan Xu
- & Junling Liu
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| Open Access
Homeostatic serum IgE is secreted by plasma cells in the thymus and enhances mast cell survival
Elevated levels of IgE is associated with a range of allergic pathology but the source of such IgE producing B cells during the steady state is poorly understood. Here, Kwon et al. show that homeostatic IgE is secreted by plasma cells in the thymus and link this to mast cell survival.
- Dong-il Kwon
- , Eun Seo Park
- & You Jeong Lee
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| Open Access
Antibody-secreting cell destiny emerges during the initial stages of B-cell activation
The development of activated B cells into antibody-secreting cells (ASC) is a critical step for humoral immunity. Here the authors show, using adoptive transfers and single cell RNA sequencing, that commitment to ASC occurs soon following B cell activation, and is coordinated by specific transcriptome programs and proliferation kinetics.
- Christopher D. Scharer
- , Dillon G. Patterson
- & Jeremy M. Boss
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| Open Access
mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion
Antibody production in plasma cells involves the unfold protein response (UPR), but how this is regulated is not clear. Here the authors show that mTORC1 signalling but not Xbp1-mediated transcription regulation in activated B cells is important for the induction of a UPR-related transcriptome that precedes full plasma cell functions.
- Brian T. Gaudette
- , Derek D. Jones
- & David Allman
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Article
| Open Access
Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR
IRE1 and PERK, both important mediators of the unfold protein response pathway, are differentially regulated during plasma cell differentiation. Here the authors show that an ufmylation target, Ufbp1, suppresses PERK to stimulate plasma cell development and is induced by the IRE1/XBP1 pathway to promote ER expansion .
- Huabin Zhu
- , Brinda Bhatt
- & Nagendra Singh
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Article
| Open Access
Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response
Long non-coding RNAs (lncRNA) constitute a large fraction of human transcriptome, and are reported, individually, for context-specific regulatory functions. Here the authors expand our understanding by providing a systemic, unbiased annotation of lncRNA to establish an atlas of lncRNA landscape during the induction of human humoral immune responses.
- Xabier Agirre
- , Cem Meydan
- & Ari Melnick
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| Open Access
IL-21 drives expansion and plasma cell differentiation of autoreactive CD11chiT-bet+ B cells in SLE
Systemic lupus erythematosus (SLE) is associated with altered B cell responses but the underlying aetiology is still unclear. Here the authors show that a CD11chiT-bet+ B cell subset with a unique phenotype and transcriptome is increased in patients with SLE, can be expanded by IL-21, and may contribute to autoimmune responses in SLE.
- Shu Wang
- , Jingya Wang
- & Rachel Ettinger
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| Open Access
Plasma cell survival in the absence of B cell memory
The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.
- Erika Hammarlund
- , Archana Thomas
- & Mark K. Slifka
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| Open Access
IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression
T cells help B cells to differentiate into antibody-producing plasma cells. Here the authors show that T cells produce interleukin-2 to activate ERK/ELK1 and suppress BACH2 expression by modulating the BACH2 super-enhancer, thereby altering BACH2 downstream transcription programs for plasma cell differentiation.
- Nicolas Hipp
- , Hannah Symington
- & Céline Delaloy
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| Open Access
Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge
Plasma cells produce secreted antibodies and are thought to lack expression of the membrane-bound immunoglobulins that constitute B-cell receptors. Here the authors show that IgM-expressing plasma cells maintain B-cell receptor expression and initiate cytokine production following antigen stimulation.
- Pascal Blanc
- , Ludovic Moro-Sibilot
- & Thierry Defrance
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| Open Access
Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection
Long-lived IgG plasma cells develop in germinal centres and then home to the bone marrow and persist for a lifetime. Here the authors identify long-lived IgM plasma cells in the murine spleen, which carry IgH mutations but can develop independently of germinal centres, and confer protective antiviral immunity.
- Caitlin Bohannon
- , Ryan Powers
- & Joshy Jacob
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Article
| Open Access
γ-secretase directly sheds the survival receptor BCMA from plasma cells
B-cell maturation antigen (BCMA) regulates the survival of B cells and is essential for the maintenance of long-lived plasma cells. Here, the authors show that γ-secretase directly sheds BCMA from the cell surface and therefore regulates the number of plasma cells.
- Sarah A. Laurent
- , Franziska S. Hoffmann
- & Edgar Meinl
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Mir-17–92 regulates bone marrow homing of plasma cells and production of immunoglobulin G2c
After activation and selection, plasma cells home to the bone marrow where they persist and continue to make antibodies. Here the authors show that the mir-17–92cluster coordinates the process by regulating the homing receptor S1PR1 and the transcription factor IKAROS that controls IgG2c production.
- Shengli Xu
- , Xijun Ou
- & Kong-Peng Lam
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Article
| Open Access
Shp1 signalling is required to establish the long-lived bone marrow plasma cell pool
SHP-1 signalling is required for the normal development of B lymphocytes but its role in the terminal differentiation of these cells has not been fully established. Here, the authors show that SHP-1 ablation impairs the establishment of long-lived bone marrow-resident plasma cells due to aberrant integrin activation.
- Yan-Feng Li
- , Shengli Xu
- & Kong-Peng Lam
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Article
| Open Access
Restricted VH/VL usage and limited mutations in gluten-specific IgA of coeliac disease lesion plasma cells
Coeliac disease is characterized by an inappropriate immune response to dietary gluten proteins, involving the production of antibodies reactive to gluten. Here, the authors study the intestinal antibody response against gluten and show that gluten-specific antibodies have a low degree of somatic hypermutations.
- Øyvind Steinsbø
- , Carole J. Henry Dunand
- & Ludvig M. Sollid
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| Open Access
Microbe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice
Intestinal plasma cells contribute to the delicate balance between immunity against pathogens and tolerance of intestinal microflora. Kunisawa et al. identify a subpopulation of plasma cells whose proliferation depends on stimulation by microbes and IL-10, and which mediate early-phase responses to oral antigens.
- Jun Kunisawa
- , Masashi Gohda
- & Hiroshi Kiyono
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In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo
In response to antigens, B cells proliferate and form germinal centres before differentiating into memory B cells or long-lived plasma cells. Here, a culture method is used to expand B cells in vitro, with the ability to shift the fate of the cells between memory B cells and long-lived plasma cells.
- Takuya Nojima
- , Kei Haniuda
- & Daisuke Kitamura
Recruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow