A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

Hao, Yi; O’Neill, Patrick J.; Naradikian, Martin S.; Scholz, Jean L.; Cancro, Michael P.

doi:10.1182/blood-2011-01-330530

Cited by 441 publications

(651 citation statements)

References 49 publications

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“…The phenotype of the T-bet-expressing B cells that are induced by TLR7 engagement and virus infections is very similar to that of a B-cell population, composed of age-associated B cells (ABCs), that we and others have previously described (19)(20)(21)36). Both the virus-specific B cells and ABCs are T-bet + CD11b + CD11c + , and both are most efficiently induced by TLR7 engagement (Fig.…”

Section: Discussionmentioning

confidence: 75%

“…S6). The joint expression by these cells of T-bet, CD11b, and CD11c is reminiscent of another population of B cells, so-called ABCs, which we and others have recently reported (19,21), a result we consider in Discussion.…”

Section: Bcr and Tlr7 Synergize To Drive T-bet Expression In B Cellsmentioning

confidence: 84%

“…The virus-specific T-betexpressing B cells are similar in their induction requirements and properties to a type of B cell that we and others have recently described, termed age-associated B cells (ABCs). This subset of B cells accumulates in aged females and autoimmune prone mice and humans and produces auto-antibody upon stimulation and is absolutely dependent on T-bet expression for its appearance (19)(20)(21). Thus, the results suggest a unique and unexpected link between antiviral responses and autoimmunity, indicating that the same type of B-cell activation may be involved in both processes.…”

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confidence: 74%

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T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance

Rubtsova

Rubtsov

Dyk

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

244

317

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IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFNγ receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B cells, which, in turn, drives expression of CD11b and CD11c on B cells. Tbet/CD11b/CD11c positive B cells appear during antiviral responses and produce high titers of antiviral IgG2a antibodies that are critical for efficient viral clearance. The results thus demonstrate a previously unknown role for T-bet expression in B cells during viral infections. Moreover, the appearance of T-bet + B cells during antiviral responses and during autoimmunity suggests a possible link between these two processes.interferon gamma | virus

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Section: Discussionmentioning

confidence: 75%

Section: Bcr and Tlr7 Synergize To Drive T-bet Expression In B Cellsmentioning

confidence: 84%

mentioning

confidence: 74%

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T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance

Rubtsova

Rubtsov

Dyk

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

244

317

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“…2c). These age/autoimmune‐associated B cells have been characterized elsewhere and will not be a primary focus of this study 17, 18, 19, 20. These data show that ageing is associated with significant dynamic changes to the frequency and number of certain B‐cell populations in the spleen.…”

Section: Resultsmentioning

confidence: 88%

Ageing adversely affects the migration and function of marginal zone B cells

Turner

Mabbott

2017

Immunology

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SummaryMarginal zone (MZ) B cells are positioned within the spleen to capture blood‐borne antigen and immune complexes and deliver them to follicular dendritic cells in the B‐cell follicles. We show that within the spleens of aged mice antigen capture by MZ B cells, and their ability to shuttle between the follicle and MZ, were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine‐1‐phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B‐cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T‐cell‐independent (TI) antibody‐responses to microbial polysaccharide antigen. In aged mice the ability to produce immunoglobulins in response to the TI type 1 antigen TNP‐LPS was impaired. These ageing‐related changes to the MZ and MZ B cells have implications for the clearance of blood‐borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI antigen, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing‐related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.

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“…B-1 and MZ cells share some characteristic features such as the oligoclonality of their BCRs (1, 2), Agindependent selection (3), their distribution in particular niches, a preactivation status that is responsible for their rapid multispecific responses (4), and their participation in maintaining homeostasis and in the initial phases of the immune response (5). Recently, several new innate like B lymphocytes have been described, such as age-associated B cells (ABCs) (6,7), gut-associated B cells (8), and innate response activator (IRA) cells (9), which are implicated in autoimmune disorders and the responses to microbial infection.…”

mentioning

confidence: 99%

Dynamics of the Splenic Innate-like CD19+CD45Rlo Cell Population from Adult Mice in Homeostatic and Activated Conditions

Andrés

Prado

Palacios

et al. 2012

The Journal of Immunology

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In the adult spleen, CD19+CD45R−/lo (19+45Rlo) lymphocytes of embryonic origin exist as a distinct population to that of the conventional B cell lineage. These cells display a plasmablast phenotype, and they spontaneously secrete IgG1 and IgA, whereas the bone marrow population of 19+45Rlo cells contains B1 progenitors. In this study, we show that 19+45Rlo cells are also present in Peyer’s patches and in the spleen throughout the life span of wild-type mice, beginning at postnatal day 7. Although this population is heterogeneous, the surface phenotype of most of these cells distinguishes them from follicular, transitional, marginal zone, and B1 cells. In CBA/CaHN mice, few 19+45Rlo cells were detected at postnatal day 7, and none was observed in the adult spleen. Splenic 19+45Rlo cells exhibited homeostatic BrdU uptake in vivo and actively transcribed cell cycle genes. When transferred to immunodeficient RAG2−/−γchain−/− recipient mice, 19+45Rlo cells survived and differentiated into IgG1– and IgA–plasma cells. Moreover, in vitro stimulation of splenic 19+45Rlo cells with LPS, CpG, BAFF/IL4, and CD40/IL4 induced cell proliferation, IgG1/IgA secretion and the release of IL-10, suggesting a potential immunoregulatory role for this subset of innate-like B cells.

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A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

Cited by 441 publications

References 49 publications

T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance

T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance

Ageing adversely affects the migration and function of marginal zone B cells

Dynamics of the Splenic Innate-like CD19+CD45Rlo Cell Population from Adult Mice in Homeostatic and Activated Conditions

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