From the fetal liver to spleen and gut: the highway to natural antibody

Rosado, Maria Manuela; Aranburu, Alaitz; Capolunghi, Federica; Giorda, Ezio; Cascioli, Simona; Cenci, Francesco; Petrini, Stefania; Miller, E. Katherine; Leanderson, Tomas; Bottazzo, G. F.; Natali, P. G.; Carsetti, Rita

doi:10.1038/mi.2009.15

Cited by 51 publications

(47 citation statements)

References 52 publications

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“…However, more ground-breaking studies with this antigen now show that it triggers the development of antigen-specific B-1 memory cells that develop in the spleen, migrate to PerC, and persist indefinitely there until rechallenge in the context of a Toll-like receptor (TLR)-4 stimulations brings them back to develop into antibodyproducing cells in the spleen (12,19). Recent studies by Carsetti and colleagues (20) demonstrate that a Hoechst-excluding "side population" that can be sorted from the spleen contains B-1 progenitors that restore mucosal IgA production and, hence, provide key protection against gut infections. Studies presented here introduce a robust phenotype for these progenitors and distinguished them from B-2 progenitors in the spleen.…”

Section: Discussionmentioning

confidence: 99%

Distinct progenitors for B-1 and B-2 cells are present in adult mouse spleen

Ghosn

Sadate-Ngatchou

Yang

et al. 2011

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

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Recent studies by Dorshkind, Yoder, and colleagues show that embryonic (E9) B-cell progenitors located in the yolk sac and intraembryonic hemogenic endothelium before the initiation of circulation give rise to B-1 and marginal zone B cells but do not give rise to B-2 cells. In studies here, we confirm and extend these findings by showing that distinct progenitors for B-1 and B-2 cells are present in the adult spleen. Furthermore, we show that the splenic B-cell progenitor population (lin -CD19 + /B220 lo/− /CD43 -) that gives rise to B-1 cells is likely to be heterogeneous because, in some recipients, it also gives rise to B cells expressing the marginal zone phenotype (B220 hi IgM hi IgD lo CD21 hi ) and to some (CD19 -CD5 hi ) T cells. In addition to the well-known function differences between B-1 and B-2, our studies demonstrate that substantial developmental differences separate these B-cell lineages. Thus, consistent with the known dependence of B-2 development on IL-7, all B-2 progenitors express IL-7R. However, >30% of the B-1 progenitors do not express this marker, enabling the known IL-7 independent development of B-1 cells in IL-7 −/− mice. In addition, marker expression on cells in the early stages of the B-2 development pathway (CD19 -/c-Kit lo/− / Sca-1 lo/− ) in adult bone marrow distinguish it from the early stages of B-1 development (CD19 hi /c-Kit + /Sca-1 + ), which occur constitutively in neonates. In adults, in vivo inflammatory stimulation (LPS) triggers B-1 progenitors in spleen to expand and initiate development along this B-1 developmental pathway. A fter many years of smoke but no clear fire, Dorshkind, Yoder, and colleagues (1) finally identified embryonic (E9) B-cell progenitors that give rise to B-1 and marginal zone (MZ) B cells in adoptive recipients, but do not give rise to B-2 cells. Located in the yolk sac and intraembryonic hemogenic endothelium before the initiation of circulation, these B-1 and MZ B progenitors predate the emergence of the well-known B-cell progenitors in the fetal liver, which collectively give rise to B-1, B-2, and MZ B cells (1-3). The fetal liver B-cell progenitors are detectable in the fetus from day 13 onwards. These progenitors start to give rise to mature IgM-bearing B cells shortly before birth and collectively continue to populate the B-cell compartments during neonatal life and beyond.

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Section: Discussionmentioning

confidence: 99%

Distinct progenitors for B-1 and B-2 cells are present in adult mouse spleen

Ghosn

Sadate-Ngatchou

Yang

et al. 2011

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

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“…Transitional B cells also give rise to the B2 B cells that form the follicular mantle in secondary lymphoid tissues. The latter are the precursors of the effector cells of the B cell arm of the adaptive immune response (Rosado et al 2009). …”

Section: B Cell Subsets In Mouse and Humanmentioning

confidence: 99%

“…Details about the cellular structure, cellular organisation, and chemokine environment in the murine marginal zone were summarised by Mebius and Kraal (2005), whereas an overview of the human marginal zone is found in Steiniger et al (2001) and Wilkins and Wright (2000). In addition to structural differences between mouse and human spleen described above, B cell development from precursors, and also maturation of the B1a B cell subsets that is associated with mucosal IgA production occurs in the spleen of mice and not in humans (Rosado et al 2009), implying a marked difference in functional capability within the structure of mouse and human spleen.…”

Section: Differences Between Mouse and Human Spleenmentioning

confidence: 99%

“…However, human splenic marginal zone B cells accumulate over the first 2 years of life (Timens et al 1989) and have somatic mutations in their immunoglobulin heavy chain variable region (IGHV) genes (Dunn-Walters et al 1995). No hypermutation of IGHV genes in transitional B cells has been described, other than the very low frequencies associated with cellular activation (Rosado et al 2009). It is difficult to see how human splenic marginal zone B cells could be derived directly by maturation alone from transitional B cell precursors, thus potentially removing the possibility of a direct differentiation step from transitional B cell to marginal zone B cell in man.…”

Section: Relationship Between Human Transitional B Cells and The Spleenmentioning

confidence: 99%

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Transitional B Cells: How Well Are the Checkpoints for Specificity Understood?

Vossenkämper

Spencer

2011

Arch. Immunol. Ther. Exp.

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It is crucial for the immune system to minimise the number of circulating mature self-reactive B cells, in order to reduce the potential for the development of autoantibody-related autoimmune diseases. Studies of animal models have identified two major checkpoints that ensure that such cells do not contribute to the naïve B cell repertoire. The first is in the bone marrow as B cells develop and the second is in the spleen; B cells that are released from the bone marrow as transitional B cells go through more stringent selection in the spleen before they develop into mature naïve B cells. Transitional B cells and their maturation have mostly been studied in mice. However, recent studies characterised human transitional B cells and found considerable differences to current models. In this review, we will consider these differences alongside known differences in mouse and human splenic function and ask whether human transitional B cells might develop along a different pathway.

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“…B-1 cells may mount intestinal TI antibody responses after migrating from the peritoneal cavity to the intestinal LP through the omentum in response to signals from microbial TLR ligands (Ha et al, 2006;Macpherson et al, 2000;Stoel et al, 2005;Rosado et al, 2009). Disagreement over the involvement of B-1 cells in intestinal antibody production might result from phenotypic changes occurring in B-1 cells following their homing to the LP (Berland and Wortis, 2002;Stoel et al, 2005;Rosado et al, 2009;Thurnheer et al, 2003).…”

Section: Ti Iga Responses In the Intestinal Lpmentioning

confidence: 94%