B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

Pedersen, Gabriel Kristian; Ádori, Mónika; Khoenkhoen, Sharesta; Dosenovic, Pia; Beutler, Bruce; Hedestam, Gunilla B. Karlsson

doi:10.1073/pnas.1415866111

Cited by 44 publications

(95 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As such, we predict that the transitional B cells we observe in the perinatal spleen are also of the B-1 lineage. Developmental differences between transitional B-1 and B-2 cells have been described (35); we therefore sought to determine whether the enhanced chemotactic response of late transitional (relative to early transitional) B cells to CXCL13 is also a characteristic of adult, bone marrow-derived B cells. To address this question, we repeated our Transwell analysis on adult splenic and blood-derived B cells (Figure 6).…”

Section: Resultsmentioning

confidence: 99%

CXCL13 Responsiveness but Not CXCR5 Expression by Late Transitional B Cells Initiates Splenic White Pulp Formation

Neely

Flajnik

2015

The Journal of Immunology

View full text Add to dashboard Cite

Secondary lymphoid organs (SLO) provide the structural framework for co-concentration of antigen and antigen-specific lymphocytes required for an efficient adaptive immune system. The spleen is the primordial SLO, and evolved concurrently with Ig/TCR:pMHC-based adaptive immunity. The earliest cellular/histological event in the ontogeny of the spleen’s lymphoid architecture, the white pulp (WP), is the accumulation of B cells around splenic vasculature, an evolutionarily conserved feature since the spleen’s emergence in early jawed vertebrates such as sharks. In mammals, B cells are indispensable for both formation and maintenance of SLO microarchitecture; their expression of lymphotoxin α1β2 (LTα1β2) is required for the LTα1β2:CXCL13 positive feedback loop without which SLO cannot properly form. Despite the spleen’s central role in the evolution of adaptive immunity, neither the initiating event nor the B cell subset necessary for WP formation has been identified. We therefore sought to identify both in mouse. We detected CXCL13 protein in late embryonic splenic vasculature, and its expression was TNFα- and RAG-2-independent. A substantial influx of CXCR5+ transitional B cells into the spleen occurred 18 hours before birth. However, these late embryonic B cells were unresponsive to CXCL13 (though responsive to CXCL12) and phenotypically indistinguishable from blood-derived B cells. Only after birth did B cells acquire CXCL13 responsiveness, accumulate around splenic vasculature, and establish the uniquely splenic B cell compartment, enriched for CXCL13-responsive late transitional cells. Thus, CXCL13 is the initiating component of the CXCL13:LTα1β2 positive feedback loop required for WP ontogeny, and CXCL13-responsive late transitional B cells are the initiating subset.

show abstract

Section: Resultsmentioning

confidence: 99%

CXCL13 Responsiveness but Not CXCR5 Expression by Late Transitional B Cells Initiates Splenic White Pulp Formation

Neely

Flajnik

2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This led them to propose that B-1 cells, similar to T cells, are positively selected based on their ability to bind to self-antigens. Further supporting strong self-antigen binding as a driver of B-1a cell development were studies that showed the lack of B-1a cell development in CD19-deficient mice (57), as well as in mice lacking either other co-stimulatory molecules (reviewed in (13)), or components of the NFkB signaling cascade (58), all defects that reduce BCR signaling. Thus, heavy usage of germline-encoded BCR, and the presence of relatively large clones of distinct, self-reactive B-1a cells develop in all mouse strains to shape the B-1 cell repertoire, possibly following BCR-stimulation by self-antigens.…”

Section: B-1 Cell Repertoire Selection and Maintenancementioning

confidence: 99%

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

Baumgarth

2017

The Journal of Immunology

105

View full text Add to dashboard Cite

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.

show abstract

“…Moreover, with increased systemic inflammation in CaSR-deficient mice, B cells in the periphery expressed CD93, a marker that is found on immature B cell precursors in the bone marrow, with much lower expression found in splenic B cells as they mature. It is re-induced during plasma cell differentiation and plays an important role in maintaining plasma cells in the bone marrow [88, 89], indicating the impact of the CaSR on these cells that maintain antibody secretion and potentially regulate the levels of plasma cells, not only in bone marrow niches, but also in the gut (Fig. 2).…”

Section: The Role Of the Casr In Secretory Diarrhea And Colitismentioning

confidence: 99%

The role of the calcium-sensing receptor in gastrointestinal inflammation

Owen

Cheng

et al. 2016

Seminars in Cell & Developmental Biology

View full text Add to dashboard Cite

The gastrointestinal (GI) tract must balance the extraction of energy and metabolic end-products from ingested nutrition and resident gut microbes and the maintenance of a symbiotic relationship with this microbiota, with the ability to mount functional immune responses to pathogenic organisms to maintain GI health. The gut epithelium is equipped with bacteria-sensing mechanisms that discriminate between pathogenic and commensal microorganisms and regulate host responses between immunity and tolerance. The epithelium also expresses numerous nutrient-sensing receptors, but their importance in the preservation of the gut microbiota and immune homeostasis remains largely unexplored. Observations that a deficiency in the extracellular calcium-sensing receptor (CaSR) using intestinal epithelium-specific receptor knockout mice resulted in diminished intestinal barrier integrity, altered composition of the gut microbiota, modified expression of intestinal pattern recognition receptors, and a skewing of local and systemic innate responses from regulatory to stimulatory, may change the way that this receptor is considered as a potential immunotherapeutic target in gut homeostasis. These findings suggest that pharmacologic CaSR activators and CaSR-based nutrients such as calcium, polyamines, phenylalanine, tryptophan, and oligo-peptides might be useful in conditioning the gut microenvironment, and thus, in the prevention and treatment of disorders such as inflammatory bowel disease (IBD), infectious enterocolitis, and other inflammatory and secretory diarrheal diseases. Here, we review the emerging roles of the CaSR in intestinal homeostasis and its therapeutic potential for gut pathology.

show abstract

B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

Cited by 44 publications

References 41 publications

CXCL13 Responsiveness but Not CXCR5 Expression by Late Transitional B Cells Initiates Splenic White Pulp Formation

CXCL13 Responsiveness but Not CXCR5 Expression by Late Transitional B Cells Initiates Splenic White Pulp Formation

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

The role of the calcium-sensing receptor in gastrointestinal inflammation

Contact Info

Product

Resources

About