Blimp-1–dependent and –independent natural antibody production by B-1 and B-1–derived plasma cells

Savage, Hannah P; Yenson, Vanessa M.; Sawhney, Sanjam S.; Mousseau, Betty; Lund, Frances E.; Baumgarth, Nicole

doi:10.1084/jem.20161122

Cited by 79 publications

(95 citation statements)

References 63 publications

(111 reference statements)

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“…Consistent with previous studies (reviewed in (80)), we found spontaneous IgM production to be restricted to bone marrow and spleen in both SPF-housed as well as germfree mice (81, 82). The study identified two distinct populations of natural AFC: B-1 cell-derived CD19- CD43+ IgM+ plasma cells (B-1PC) and CD19+ CD43+ IgM+ B-1 cells (82). Both cell populations contributed significantly to natural antibody production.…”

Section: B-1 Cell Regulation and Functionssupporting

confidence: 92%

“…Further analysis suggested that these B-1 cells develop into AFC without terminal differentiation (82), which is consistent with reduced but not absent serum IgM levels and normal serum levels IgG3 in mice with a B cells-specific deletion of prdm1 , the gene encoding Blimp-1 and shown to be a master regulator of B cell differentiation. The above-described effects of IL-5 on natural IgM and IgG3 may only affect the Blimp-1 dependent arm of natural antibody production, as IL-5 induces Blimp-1 expression (79), which could explain why natural IgM and IgG3 production is reduced but not gone in the absence of IL-5.…”

Section: B-1 Cell Regulation and Functionsmentioning

confidence: 54%

“…( A ) In steady state B-1 cells and B-1 cell-derived plasma cells in the spleen and bone marrow generate natural antibody, mostly IgM (81, 82). ( B ) B-1 cells make the majority B cell population in the peritoneal and pleural cavities.…”

Section: Figurementioning

confidence: 99%

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A Hard(y) Look at B-1 Cell Development and Function

Baumgarth

2017

The Journal of Immunology

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112

105

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A small population of B cells exists in lymphoid tissues and body cavities of mice that is distinct in development, phenotype and function from the majority (B-2) B cell population. This population, originally termed “Ly1” and now “B-1”, has received renewed interest as an innate-like B cell population of fetal-derived hematopoiesis, responsible for natural antibody production and rapid immune responses. Molecular analyses have begun to define fetal and adult hematopoiesis, while cell-fate mapping studies have revealed complex developmental origins of B-1 cells. Together the studies provide a more detailed understanding of B-1 cell regulation and function. This review outlines studies that defined B-1 cells as natural antibody and cytokine-producing B cells of fetal origin, with a focus on work conducted by Randy Hardy, an early pioneer and co-discoverer of B-1 cells, whose seminal contributions enhanced our understand of this enigmatic B cell population.

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Section: B-1 Cell Regulation and Functionssupporting

confidence: 92%

Section: B-1 Cell Regulation and Functionsmentioning

confidence: 54%

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A Hard(y) Look at B-1 Cell Development and Function

Baumgarth

2017

The Journal of Immunology

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112

105

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“…Additionally, the B1b subset generates anti-PPS Abs that contribute to adaptive immunity to systemic infection by S. pneumoniae (11, 55). Some experimental systems indicate that B1 cells can secrete Abs without adopting the canonical ASC phenotype (59), and if this transition to secreting cells does not require cell division, it might be expected to be relatively radioresistant. Hence, we also cannot rule out the possibility that a population of radioresistant B1b cells contributes to a postexposure memory response.…”

Section: Discussionmentioning

confidence: 99%

Nasopharyngeal Exposure to Streptococcus pneumoniae Induces Extended Age-Dependent Protection against Pulmonary Infection Mediated by Antibodies and CD138+ Cells

Ghanem

Maung

Siwapornchai

et al. 2018

The Journal of Immunology

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Streptococcus pneumoniae commonly resides asymptomatically in the nasopharyngeal (NP) cavity of healthy individuals but can cause life-threatening pulmonary and systemic infections, particularly in the elderly. NP colonization results in a robust immune response that protects against invasive infections. However, the duration, mechanism, and cellular component of such responses are poorly understood. In this study, we found that repeated NP exposure of mice to S. pneumoniae TIGR4 strain results in pneumococcal-specific Ab responses that protect against lethal lung challenge. Abs were necessary and sufficient for protection because Ab-deficient μMT mice did not develop postexposure protection, only becoming resistant to lung infection after transfer of immune sera from NP-exposed mice. T cells contributed to immunity at the time of NP exposure, but neither CD4+ nor CD8+ T cells were required. The protective activity was detectable 20 wk after exposure and was maintained in irradiated mice, suggesting involvement of long-lived Ab-secreting cells (ASC), which are radioresistant and secrete Abs for extended periods of time in the absence of T cells or persistent Ag. CD138+ bone marrow cells, likely corresponding to long-lived ASC, were sufficient to confer protection. NP exposure of aged mice failed to protect against subsequent lung infection despite eliciting a robust Ab response. Furthermore, transfer of CD138+ bone marrow cells or sera from NP-exposed old mice failed to protect naive young mice. These findings suggest that NP exposure elicits extended protection against pneumococcal lung infection by generating long-lived CD138+ ASC and that the protective efficacy of these responses declines with age.

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“…Natural serum IgM, like precursor B-1a cells, harbors autoreactivity, as well as cross-reactivity to bacterial polysaccharides, and it plays an important role in modulating the early immune response to infection and maintaining tissue homeostasis by opsonizing cell debris and oxidized low-density lipoprotein cholesterol for clearance (3). B-1a–derived IgM Ab-secreting cells (ASCs) with heterogeneous phenotypes have been identified in the BM and spleen (4). B-1a cells are maintained in a quiescent state in the face of chronic self-antigen stimulation, in part by constitutive expression of inhibitory coreceptors that suppress BCR signaling (5–8).…”

Section: Introductionmentioning

confidence: 99%

Nur77 Is Upregulated in B-1a Cells by Chronic Self-Antigen Stimulation and Limits Generation of Natural IgM Plasma Cells

et al. 2017

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B-1a cells are a unique population of innate-like B cells with a highly restricted and self-reactive BCR repertoire. Preimmune “natural” IgM produced by B-1a–derived plasma cells is essential for homeostatic clearance of cellular debris and forms a primary layer of protection against infection. In this study, we take advantage of a fluorescent reporter of BCR signaling to show that expression of the orphan nuclear hormone receptor Nur77 is upregulated under steady-state conditions in self-reactive B-1a cells in response to chronic Ag stimulation. Nur77-deficient mice exhibit elevated natural serum IgM (but not IgG) and marked expansion of IgM plasma cells of B-1a origin. Moreover, we show that Nur77 restrains the turnover of B-1a cells and the accumulation of immature IgM plasma cells. Thus, we identify a new critical negative-regulatory pathway that serves to maintain B-1a cells in a quiescent state in the face of chronic endogenous Ag stimulation.

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Blimp-1–dependent and –independent natural antibody production by B-1 and B-1–derived plasma cells

Cited by 79 publications

References 63 publications

A Hard(y) Look at B-1 Cell Development and Function

A Hard(y) Look at B-1 Cell Development and Function

Nasopharyngeal Exposure to Streptococcus pneumoniae Induces Extended Age-Dependent Protection against Pulmonary Infection Mediated by Antibodies and CD138+ Cells

Nur77 Is Upregulated in B-1a Cells by Chronic Self-Antigen Stimulation and Limits Generation of Natural IgM Plasma Cells

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