The ageing B cell population: Composition and function

We have previously characterized a human blood CD19+CD1c+IgM+CD27+CD21loCD10+ innate-like B-cell population, which presents features shared by both transitional immature and marginal zone (MZ) B-cells, named herein “precursor-like” MZ B-cells. B-cells with similar attributes have been associated with regulatory potential (Breg). In order to clarify this issue and better characterize this population, we have proceeded to RNA-Seq transcriptome profiling of mature MZ and precursor-like MZ B-cells taken from the blood of healthy donors. We report that ex vivo mature MZ and precursor-like MZ B-cells express transcripts for the immunoregulatory marker CD83 and nuclear receptors NR4A1, 2, and 3, known to be associated with T-cell regulatory (Treg) maintenance and function. Breg associated markers such as CD39 and CD73 were also expressed by both populations. We also show that human blood and tonsillar precursor-like MZ B-cells were the main B-cell population to express elevated levels of CD83 and NR4A1-3 proteins ex vivo and without stimulation. Sorted tonsillar precursor-like MZ B-cells exerted regulatory activity on autologous activated CD4+ T-cells, and this was affected by a CD83 blocking reagent. We believe these observations shed light on the Breg potential of MZ populations, and identify NR4A1-3 as potential Breg markers, which as for Tregs, may be involved in stabilization of a regulatory status. Since expression and activity of these molecules can be modulated therapeutically, our findings may be useful in strategies aiming at modulation of Breg responses.

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TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients

Arthritis Research & Therapy ◽

10.1186/s13075-016-1213-9 ◽

2017 ◽

Vol 19 (1) ◽

Cited By ~ 32

Author(s):

Octavio Aravena ◽

Ashley Ferrier ◽

Madhvi Menon ◽

Claudia Mauri ◽

Juan Carlos Aguillón ◽

...

Keyword(s):

Systemic Sclerosis ◽

B Cell ◽

Cell Population ◽

Regulatory B Cell ◽

And Function

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B Lymphocytes Producing Demyelinating Autoantibodies: Development and Function in Gene-targeted Transgenic Mice

Journal of Experimental Medicine ◽

10.1084/jem.188.1.169 ◽

1998 ◽

Vol 188 (1) ◽

pp. 169-180 ◽

Cited By ~ 163

Author(s):

Tobias Litzenburger ◽

Reinhard Fässler ◽

Jan Bauer ◽

Hans Lassmann ◽

Christopher Linington ◽

...

Keyword(s):

B Cells ◽

Transgenic Mice ◽

B Cell ◽

Cell Population ◽

Plasma Cells ◽

Autoimmune Encephalitis ◽

Normal Numbers ◽

Self Tolerance ◽

Normal Differentiation ◽

And Function

We studied the cellular basis of self tolerance of B cells specific for brain autoantigens using transgenic mice engineered to produce high titers of autoantibodies against the myelin oligodendrocyte glycoprotein (MOG), a surface component of central nervous system myelin. We generated “knock-in” mice by replacing the germline JH locus with the rearranged immunoglobulin (Ig) H chain variable (V) gene of a pathogenic MOG-specific monoclonal antibody. In the transgenic mice, conventional B cells reach normal numbers in bone marrow and periphery and express exclusively transgenic H chains, resulting in high titers of MOG-specific serum Igs. Additionally, about one third of transgenic B cells bind MOG, thus demonstrating the absence of active tolerization. Furthermore, peritoneal B-1 lymphocytes are strongly depleted. Upon immunization with MOG, the mature transgenic B cell population undergoes normal differentiation to plasma cells secreting MOG-specific IgG antibodies, during which both Ig isotype switching and somatic mutation occur. In naive transgenic mice, the presence of this substantial autoreactive B cell population is benign, and the mice fail to develop either spontaneous neurological disease or pathological evidence of demyelination. However, the presence of the transgene both accelerates and exacerbates experimental autoimmune encephalitis, irrespective of the identity of the initial autoimmune insult.

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Decision letter for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v2/decision1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Review for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v1/review1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

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Faculty Opinions recommendation of Promotion of B cell immune responses via an alum-induced myeloid cell population.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1019734.222544 ◽

2004 ◽

Author(s):

Richard Locksley

Keyword(s):

Immune Responses ◽

B Cell ◽

Cell Population ◽

Myeloid Cell

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Faculty Opinions recommendation of Evidence of early B-cell dysregulation in simian immunodeficiency virus infection: rapid depletion of naïve and memory B-cell subsets with delayed reconstitution of the naïve B-cell population.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3317956.3004055 ◽

2010 ◽

Author(s):

Willy Bogers

Keyword(s):

Virus Infection ◽

B Cell ◽

Simian Immunodeficiency Virus ◽

Cell Population ◽

Simian Immunodeficiency Virus Infection ◽

Memory B Cell ◽

Immunodeficiency Virus ◽

B Cell Subsets

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Hide and seek: interplay between influenza viruses and B cells

International Immunology ◽

10.1093/intimm/dxaa028 ◽

2020 ◽

Vol 32 (9) ◽

pp. 605-611 ◽

Cited By ~ 2

Author(s):

Masayuki Kuraoka ◽

Yu Adachi ◽

Yoshimasa Takahashi

Keyword(s):

B Cells ◽

B Cell ◽

Surface Protein ◽

Influenza Viruses ◽

Influenza Vaccines ◽

Native Structure ◽

Humoral Immune ◽

Protective Antibodies ◽

Major Surface ◽

And Function

Abstract Influenza virus constantly acquires genetic mutations/reassortment in the major surface protein, hemagglutinin (HA), resulting in the generation of strains with antigenic variations. There are, however, HA epitopes that are conserved across influenza viruses and are targeted by broadly protective antibodies. A goal for the next-generation influenza vaccines is to stimulate B-cell responses against such conserved epitopes in order to provide broad protection against divergent influenza viruses. Broadly protective B cells, however, are not easily activated by HA antigens with native structure, because the virus has multiple strategies to escape from the humoral immune responses directed to the conserved epitopes. One such strategy is to hide the conserved epitopes from the B-cell surveillance by steric hindrance. Technical advancement in the analysis of the human B-cell antigen receptor (BCR) repertoire has dissected the BCRs to HA epitopes that are hidden in the native structure but are targeted by broadly protective antibodies. We describe here the characterization and function of broadly protective antibodies and strategies that enable B cells to seek these hidden epitopes, with potential implications for the development of universal influenza vaccines.

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WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function

Blood ◽

10.1182/blood-2008-02-140715 ◽

2008 ◽

Vol 112 (10) ◽

pp. 4139-4147 ◽

Cited By ~ 71

Author(s):

Lisa S. Westerberg ◽

Miguel A. de la Fuente ◽

Fredrik Wermeling ◽

Hans D. Ochs ◽

Mikael C. I. Karlsson ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Marginal Zone ◽

Hematopoietic Cells ◽

Selective Advantage ◽

Relative Contribution ◽

B Cell Homeostasis ◽

And Function

Abstract Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4+ and CD8+ T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP−/− mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of “natural” IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance.

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