Human IgG2- and IgG4-expressing memory B cells display enhanced molecular and phenotypic signs of maturity and accumulate with age.

Abstract:

:The mechanisms involved in sequential immunoglobulin G (IgG) class switching are still largely unknown. Sequential IG class switching is linked to higher levels of somatic hypermutation (SHM) in vivo, but it remains unclear if these are generated temporally during an immune response or upon activation in a secondary response. We here aimed to uncouple these processes and to distinguish memory B cells from primary and secondary immune responses. SHM levels and IgG subclasses were studied with 454 pyrosequencing on blood mononuclear cells from young children and adults as models for primary and secondary immunological memory. Additional sequencing and detailed immunophenotyping with IgG subclass-specific antibodies was performed on purified IgG+ memory B-cell subsets. In both children and adults, SHM levels were higher in transcripts involving more downstream-located IGHG genes (esp. IGHG2 and IGHG4). In adults, SHM levels were significantly higher than in children, and downstream IGHG genes were more frequently utilized. This was associated with increased frequencies of CD27+IgG+ memory B cells, which contained higher levels of SHM, more IGHG2 usage, and higher expression levels of activation markers than CD27-IgG+ memory B cells. We conclude that secondary immunological memory accumulates with age and these memory B cells express CD27, high levels of activation markers, and carry high SHM levels and frequent usage of IGHG2. These new insights contribute to our understanding of sequential IgG subclass switching and show a potential relevance of using serum IgG2 levels or numbers of IgG2-expressing B cells as markers for efficient generation of memory responses.

journal_name

Immunol Cell Biol

authors

de Jong BG,IJspeert H,Marques L,van der Burg M,van Dongen JJ,Loos BG,van Zelm MC

doi

10.1038/icb.2017.43

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

744-752

issue

9

eissn

0818-9641

issn

1440-1711

pii

icb201743

journal_volume

95

pub_type

杂志文章
  • Nasal vaccination stimulates CD8(+) T cells for potent protection against mucosal Brucella melitensis challenge.

    abstract::Brucellosis remains a significant zoonotic threat worldwide. Humans and animals acquire infection via their oropharynx and upper respiratory tract following oral or aerosol exposure. After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventio...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2016.5

    authors: Clapp B,Yang X,Thornburg T,Walters N,Pascual DW

    更新日期:2016-05-01 00:00:00

  • Plasmacytoid dendritic cells from parent strains of the NZB/W F1 lupus mouse contribute different characteristics to autoimmune propensity.

    abstract::The NZB/W F1 (F1) mice develop severe disease that is similar to human systemic lupus erythematosus. By contrast, each parent strain, NZB or NZW, has limited autoimmunity, suggesting traits of both strains contribute to pathogenesis. Although many of the contributing genes have been identified, the contributing cellul...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/imcb.12313

    authors: Zhan Y,Kong I,Chopin M,Macri C,Zhang JG,Xie J,Nutt SL,O'Keeffe M,Hawkins ED,Morand EF,Lew AM

    更新日期:2020-03-01 00:00:00

  • Tumour necrosis factor and lymphotoxin: molecular aspects and role in tissue-specific autoimmunity.

    abstract::Tumour necrosis factor (TNF) is a highly potent, proinflammatory cytokine with broad-ranging functions from the regulation of endothelial cell adhesion molecules to facilitate entry of leucocytes into tissues, to direct induction of cellular cytotoxicity. This diversity of function potentially attributable to TNF in t...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/icb.1996.77

    authors: Körner H,Sedgwick JD

    更新日期:1996-10-01 00:00:00

  • Separate roles of IL-6 and oncostatin M in mouse macrophage polarization in vitro and in vivo.

    abstract::Arginase-1 (Arg-1)-expressing M2-like macrophages are associated with Th2-skewed immune responses, allergic airway pathology, ectopic B16 melanoma cancer growth in murine models, and can be induced by Oncostatin M (OSM) transient overexpression in vivo. Here, we compare OSM to the gp130-cytokine IL-6 in mediating macr...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/imcb.1035

    authors: Dubey A,Izakelian L,Ayaub EA,Ho L,Stephenson K,Wong S,Kwofie K,Austin RC,Botelho F,Ask K,Richards CD

    更新日期:2018-03-01 00:00:00

  • Identification of mature plasma cells in early rat yolk sac. A possible origin from the endodermal cell layer: immunohistochemistry and immunoelectron microscopic study.

    abstract::Plasma cells play a pivotal role in the immune system and are responsible for the synthesis and release of immunoglobulins. Numerous in vitro culture experiments on the yolk sac demonstrated the generation of mature cells of the myeloid and lymphoid lineages under appropriate culture conditions. However, there are no ...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1711.2003.t01-1-01178.x

    authors: El-Nefiawy N,Abdel-Hakim K,Kanayama N,Suganuma N,Terao T

    更新日期:2003-10-01 00:00:00

  • Embryonic macrophages of early rat yolk sac: Immunohistochemistry and ultrastructure with reference to endodermal cell layer.

    abstract::Macrophages are multifunctional cells that participate in numerous biological processes; they actively phagocytose foreign particles and cell debris. Embryonic tissue macrophages are present at early stages of mammalian development; their ontogeny and function is still under investigation. Our study used immunohistoch...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1711.2002.01109.x

    authors: El-Nefiawy N,Abdel-Hakim K,Yamashita A,Kanayama N

    更新日期:2002-10-01 00:00:00

  • Protection against non-typable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: role of specific antibody and phagocytes.

    abstract::Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose-response experiments demonstrated that while lowering the dose of non-t...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.1995.42

    authors: Wallace FJ,Witt CS,Clancy RL,Cripps AW

    更新日期:1995-06-01 00:00:00

  • Rationally designed capsid and transgene cassette of AAV6 vectors for dendritic cell-based cancer immunotherapy.

    abstract::Dendritic cell (DC)-based immunotherapy has recently demonstrated a great potential for clinical applications; however, additional progress in the methods of tumor-specific antigen delivery to DCs is necessary for the further development of anti-tumor vaccines. To this end, a capsid-optimized adeno-associated virus se...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2013.74

    authors: Pandya J,Ortiz L,Ling C,Rivers AE,Aslanidi G

    更新日期:2014-02-01 00:00:00

  • Exogenous, TAP-independent lysosomal presentation of a respiratory syncytial virus CTL epitope.

    abstract::Respiratory syncytial virus causes lower respiratory tract infections in infancy and old age, affecting also immunocompromised patients. The viral fusion protein is an important vaccine candidate eliciting antibody and cell-mediated immune responses. CD8(+) cytotoxic T lymphocytes (CTLs) are known to have a role in bo...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2012.43

    authors: Johnstone C,Ramos M,García-Barreno B,López D,Melero JA,Del Val M

    更新日期:2012-11-01 00:00:00

  • Neuronal antigens modulate the immune response associated with experimental autoimmune encephalomyelitis.

    abstract::Rats primed with bovine myelin (BM) in complete Freunds adjuvant, develop acute experimental autoimmune encephalomyelitis (EAE). We have previously described that intraperitoneal administration prior to the active induction of the disease of a bovine synaptosomal fraction (BSF) and BM were effective ways of suppressin...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1711.2004.01200.x

    authors: Degano AL,Ditamo Y,Roth GA

    更新日期:2004-02-01 00:00:00

  • mTORC1 signaling is crucial for regulatory T cells to suppress macrophage-mediated inflammatory response after acute myocardial infarction.

    abstract::Post-infarction inflammatory response results in worse remodeling and dysfunction following myocardial infarction (MI). Supression of post-infarction inflammation would be a logical approach of alleviating post-infarction injury and promoting cardiac repair. In this study, we investigated the significance of mTORC1 si...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2015.88

    authors: Yang K,Zhang Y,Xu C,Li X,Li D

    更新日期:2016-03-01 00:00:00

  • Prokaryotic RNA activates endothelial cells promoting neutrophil transmigration.

    abstract::Endothelial cell (EC)-neutrophil (PMN) interactions are crucial in the resolution of bacterial infections. Prokaryotic RNA (pRNA) has been reported as a pathogen-associated molecular pattern that is released from bacteria upon death and is able to activate PMN. In this work, we studied the effects of pRNA on EC and in...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/imcb.12282

    authors: Castillo LA,Birnberg Weiss F,Rodriguez-Rodrigues N,Pittaluga JR,Martire-Greco D,Milillo MA,Grinstein SF,Camelli MR,Mena Aybar AJ,Landoni VI,Fernández GC

    更新日期:2019-10-01 00:00:00

  • CD49b-dependent establishment of T helper cell memory.

    abstract::CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2013.36

    authors: Hanazawa A,Hayashizaki K,Shinoda K,Yagita H,Okumura K,Löhning M,Hara T,Tani-ichi S,Ikuta K,Eckes B,Radbruch A,Tokoyoda K,Nakayama T

    更新日期:2013-09-01 00:00:00

  • Lethal giant larvae-1 deficiency enhances the CD8(+) effector T-cell response to antigen challenge in vivo.

    abstract::Lethal giant larvae-1 (Lgl-1) is an evolutionary conserved protein that regulates cell polarity in diverse lineages; however, the role of Lgl-1 in the polarity and function of immune cells remains to be elucidated. To assess the role of Lgl-1 in T cells, we generated chimeric mice with a hematopoietic system deficient...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2015.82

    authors: Ramsbottom KM,Sacirbegovic F,Hawkins ED,Kallies A,Belz GT,Van Ham V,Haynes NM,Durrant MJ,Humbert PO,Russell SM,Oliaro J

    更新日期:2016-03-01 00:00:00

  • Ficolin A derived from local macrophages and neutrophils protects against lipopolysaccharide-induced acute lung injury by activating complement.

    abstract::Ficolins are important and widely distributed pattern recognition molecules that can induce lectin complement pathway activation and initiate the innate immune response. Although ficolins can bind lipopolysaccharide (LPS) in vitro, the sources, dynamic changes and roles of local ficolins in LPS-induced pulmonary infla...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/imcb.12344

    authors: Wu X,Yao D,Bao L,Liu D,Xu X,An Y,Zhang X,Cao B

    更新日期:2020-08-01 00:00:00

  • Regulation of neural stem cell differentiation in the forebrain.

    abstract::In the developing forebrain, mounting evidence suggests that neural stem cell proliferation and differentiation is regulated by growth factors. In vitro in the presence of serum, stem cell proliferation is predominantly mediated by fibroblast growth factor-2 (FGF-2) whereas neuronal differentiation can be triggered by...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1711.1998.00762.x

    authors: Bartlett PF,Brooker GJ,Faux CH,Dutton R,Murphy M,Turnley A,Kilpatrick TJ

    更新日期:1998-10-01 00:00:00

  • Interactions of tunicate immunomodulatory proteins with mammalian cells.

    abstract::The ability of a tunicate immunomodulatory protein, tunIL1, to interact with mammalian cells was investigated. TunIL1 is known to regulate inflammatory defence reactions in tunicates and to stimulate the proliferation of mammalian thymocytes. In the current study, tunIL1 was shown to enchance L929 fibroblast prolifera...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.1996.3

    authors: Raftos D

    更新日期:1996-02-01 00:00:00

  • Retinoic acid suppresses IL-17 production and pathogenic activity of γδ T cells in CNS autoimmunity.

    abstract::Retinoic acid (RA) in the steady state enhances induction of Foxp3(+) regulatory T (Treg) cells and inhibits differentiation of Th1 and Th17 cells, thereby maintaining tolerance, but can in inflammatory conditions promote effector Th1 and Th17 cells that mediate inflammation. IL-17-producing γδ T cells have recently b...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2016.39

    authors: Raverdeau M,Breen CJ,Misiak A,Mills KH

    更新日期:2016-09-01 00:00:00

  • Dendritic cells and humoral immunity in humans.

    abstract::Dendritic cells (DCs) orchestrate the innate and adaptive immune systems to induce tolerance and immunity. DC plasticity and subsets are prominent determinants in the regulation of immune responses. Our recent studies suggest that humoral and cellular immunity is regulated by different myeloid DC subsets with distinct...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/icb.2010.28

    authors: Ueno H,Schmitt N,Palucka AK,Banchereau J

    更新日期:2010-05-01 00:00:00

  • Inactivation of CD4+ CD25+ regulatory T cells during early mycobacterial infection increases cytokine production but does not affect pathogen load.

    abstract::Mycobacterium tuberculosis uses numerous mechanisms to avoid elimination by the infected host. In this study, we investigated the possibility whether, similar to other pathogens, M. tuberculosis exploits natural CD4+ CD25+ T-regulatory cells (Treg) to suppress the effector function of responding host lymphocytes, thus...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/j.1440-1711.2006.01460.x

    authors: Quinn KM,McHugh RS,Rich FJ,Goldsack LM,de Lisle GW,Buddle BM,Delahunt B,Kirman JR

    更新日期:2006-10-01 00:00:00

  • Mycoplasma infection can sensitize host cells to apoptosis through contribution of apoptotic-like endonuclease(s).

    abstract::Mycoplasma infection may lead to various pathologies in a broad range of hosts. It has been shown that Mycoplasma may trigger cell death in cell cultures; however, the mechanism remains unknown. In the present paper we show that Mycoplasma infection of different lymphocyte and epithelial tumour cell lines leads to the...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1046/j.1440-1711.1998.00781.x

    authors: Sokolova IA,Vaughan AT,Khodarev NN

    更新日期:1998-12-01 00:00:00

  • Fluorescent dyes for lymphocyte migration and proliferation studies.

    abstract::Fluorescent dyes are increasingly being exploited to track lymphocyte migration and proliferation. The present paper reviews the properties and performance of some 14 different fluorescent dyes that have been used during the last 20 years to monitor lymphocyte migration. Of the 14 dyes discussed, two stand out as bein...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1440-1711.1999.00877.x

    authors: Parish CR

    更新日期:1999-12-01 00:00:00

  • Special feature for the Olympics: effects of exercise on the immune system: neuropeptides and their interaction with exercise and immune function.

    abstract::It is known today that the immune system is influenced by various types of psychological and physiological stressors, including physical activity. It is well known that physical activity can influence neuropeptide levels both in the central nervous system as well as in peripheral blood. The reported changes of immune ...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1440-1711.2000.t01-10-.x

    authors: Jonsdottir IH

    更新日期:2000-10-01 00:00:00

  • Development of prophylactic and therapeutic vaccines using the ISCOMATRIX adjuvant.

    abstract::Adjuvants are components that when added to subunit antigen (Ag) vaccines boost their immunogenicity and thus immune efficacy. However, there are few adjuvants that are approved for clinical use resulting in a critical need for the development of safe and effective adjuvants for use in both prophylactic and therapeuti...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/icb.2009.21

    authors: Maraskovsky E,Schnurr M,Wilson NS,Robson NC,Boyle J,Drane D

    更新日期:2009-07-01 00:00:00

  • TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution.

    abstract::The utility of T-cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination-activating gene (RAG)-1 or RAG-2 knockouts is frequently used ...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1111/imcb.12033

    authors: McGuire HM,Watkins TS,Field M,Taylor S,Yasuyama N,Farmer A,Miles JJ,Fazekas de St Groth B

    更新日期:2018-07-01 00:00:00

  • Polyinosinic-polycytidylic acid inhibits the differentiation of mouse preadipocytes through pattern recognition receptor-mediated secretion of tumor necrosis factor-α.

    abstract::Viral infections can disturb the functions of adipose tissues and thus result in metabolic diseases. Polyinosinic-polycytidylic acid (poly(I:C)), a synthetic analog of viral double-stranded RNA, induces innate antiviral responses by mimicking viral infection through the activation of pattern recognition receptors (PRR...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2016.57

    authors: Yu L,Liu G,Yang C,Song X,Wang H

    更新日期:2016-10-01 00:00:00

  • Humoral immune responses in mice using gamma inulin preparations as adjuvants for hepatitis B vaccines.

    abstract::There is an urgent need for new, powerful adjuvants suitable for use with sub-unit and peptide vaccines in humans. We have measured the humoral immune response in BALB/c mice to vaccine formulations using recombinant HBsAg antigens, and gamma inulin and alum adjuvants. Using Merck, Sharpe & Dohme (MSD) HBsAg at 10 mic...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.1990.15

    authors: Leslie DE,Nicholson S,Dimitrakakis M,Johnston N,Gust ID

    更新日期:1990-04-01 00:00:00

  • TLR3 drives IRF6-dependent IL-23p19 expression and p19/EBI3 heterodimer formation in keratinocytes.

    abstract::Interferon regulatory factor (IRF) family members impart cell-type specificity to toll-like receptor (TLR) signalling, and we recently identified a role for IRF6 in TLR2 signalling in epithelial cells. TLR3 has a well-characterized role in wound healing in the skin, and here, we examined TLR3-dependent IRF6 functions ...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.2015.77

    authors: Ramnath D,Tunny K,Hohenhaus DM,Pitts CM,Bergot AS,Hogarth PM,Hamilton JA,Kapetanovic R,Sturm RA,Scholz GM,Sweet MJ

    更新日期:2015-10-01 00:00:00

  • An evolution-based hypothesis on the origin and mechanisms of autoimmune disease.

    abstract::The pathogenesis of autoimmune disease remains an enigma. Here, the condition is analysed from an evolutionary standpoint, and the thesis developed that viruses, in particular retroviruses, are important to our evolution, and that their inappropriate re-expression by repetitive (? ischaemic) cell damage in individuals...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/icb.1997.78

    authors: Boyd GW

    更新日期:1997-10-01 00:00:00

  • Establishment of a natural suppressor cell line producing soluble suppressor factor other than transforming growth factor-beta.

    abstract::Natural suppressor (NS) cell line (Clone 59) was established from the bone marrow of adult C3H/Hej mice in the presence of WEHI-3 conditioned media. Clone 59 cells suppressed the generation of cytotoxic T lymphocytes from normal mouse spleen. This suppression was seen at a responder-to-suppressor cell ratio of 1000:1 ...

    journal_title:Immunology and cell biology

    pub_type: 杂志文章

    doi:10.1038/icb.1995.51

    authors: Yanagië H,Sugiyama H,Sekiguchi M

    更新日期:1995-08-01 00:00:00