APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells

Belnoue, Elodie; Pihlgren, Maria; McGaha, Tracy L.; Tougne, Chantal; Rochat, Anne Frangoise; Bossen, Claudia; Schneider, Pascal; Huard, Bertrand; Lambert, Paul Henri; Siegrist, Claire Anne

doi:10.1182/blood-2007-09-110858

Cited by 316 publications

(281 citation statements)

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“…Conversely, the use of blocking reagents concluded that either APRIL or BAFF could support PC survival (21,22). We reported the role of APRIL-producing BM Gr1 int CD11b + cells in the support of BMPCs, referring to these cells as resident BM monocytes (11). However, these cells are a heterogeneous population including monocytes, neutrophil precursors, and eosinophils, which were recently claimed as being the major source of APRIL and IL-6 (12).…”

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confidence: 94%

“…This postulate has, however, not been experimentally tested. Lastly, both BAFF and APRIL support PC survival (11,20) in vitro. A critical in vivo role of APRIL, but not BAFF, was demonstrated using APRIL 2/2 and BAFF 2/2 mice (11).…”

mentioning

confidence: 99%

“…Several different BM cell types have recently been claimed as providing critical contributions to BMPC survival, including reticular stromal cells (7,8), osteoblasts (9), osteoclasts (10), Gr1 int CD11b + monocytes (11), eosinophils (12), megakaryocytes (MGKs) (13), and basophils (14). CXCL12-abundant reticular (CAR) cells, CXCL12 + reticular cells, and osteoblasts (15) were unambiguously demonstrated as key compartments of the BMPC niche when it was demonstrated that PCs lacking CXCR4 (the receptor for CXCL12) fail to home to the BM compartment (7).…”

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confidence: 99%

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Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Belnoue

Tougne²,

Rochat³

et al. 2012

The Journal of Immunology

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According to commonly held concepts, plasma cell (PC) longevity in bone marrow (BM) depends upon their access to survival niches. These are thought to exist in nursery cell types, which support PCs by secreting PC survival factors. To better define PC survival niches and their functioning, we adoptively transferred traceable Blimp-1-GFP PCs into recipient mice lacking a proliferation-inducing ligand (APRIL), IL-6, or macrophage migration inhibitory factor. Transferred BMPCs were preferentially associated with Ly-6Chigh monocytes (normalized colocalization index: 9.84), eosinophils (4.29), and megakaryocytes (2.12). Although APRIL was essential for BMPC survival, PC recruitment into the proximity of nursery cells was unimpaired in APRIL-deficient mice, questioning the concept that the same factors account for attraction/retention of PCs as for their local survival. Rather, the order of colocalization with BMPCs (monocytes > eosinophils > megakaryocytes) reflected these cells’ relative expression of CXCR4, VLA-4, and LFA-1, the homing and adhesion molecules that direct/retain PCs in the BM. This suggests a scenario wherein the cellular composition of the BMPC niche is defined by a common pattern of attraction/retention on CXCL12-abundant reticular docking cells. Thereby, PCs are directed to associate in a functional BM niche with hematopoietic CXCR4+VLA-4+LFA-1+ nursery cells, which provide PC survival factors.

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confidence: 94%

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confidence: 99%

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confidence: 99%

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Homing and Adhesion Patterns Determine the Cellular Composition of the Bone Marrow Plasma Cell Niche

Belnoue

Tougne²,

Rochat³

et al. 2012

The Journal of Immunology

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“…La présence des neutrophiles dans ces organes ainsi que la production d'APRIL par l'épithélium requièrent la présence d'un pathogène. Un rôle d'APRIL pour la survie des plasmocytes a été aussi éta-bli récemment au niveau de la moelle osseuse [14]. Dans ce tissu, la production d'APRIL est constitutive, assurée par les précurseurs des polynucléaires en voie de maturation ou déjà matures.…”

Section: Des Niches Riches En April Pour Les Plasmocytesunclassified

“…Il n'est pas sûr que BAFF partage avec APRIL le rôle de survie pour les plasmocytes qu'on lui a attribué [15]. En effet, la survie des plasmocytes dans la moelle osseuse n'est pas affectée par l'absence de BAFF [14]. De plus, les plasmocytes n'expriment ni BAFF-R ni TACI, mais seulement BCMA, qui possède une affinité nettement supérieure pour APRIL que pour BAFF [16].…”

Section: Des Niches Riches En April Pour Les Plasmocytesunclassified