title: Homing and adhesion patterns determine the cellular composition of the bone marrow plasma cell niche.
abstract: 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-6C(high) 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.
authors.affiliation: Department of Pathology-Immunology, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva, CH-1211 Geneva 4, Switzerland. elodie.belnoue@unige.ch
authors.forename: Elodie
authors.initials: E
authors.lastname: Belnoue
authors.forename: Chantal
authors.initials: C
authors.lastname: Tougne
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Rochat
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Pinschewer
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D002470:Cell Survival; D006412:Hematopoietic Stem Cells; D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D010950:Plasma Cells / Q000166:cytology* / Q000637:transplantation; D019718:Receptors, CXCR4; D055153:Stem Cell Niche
chemical_list: D039041:Integrin alpha4beta1; D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4