title: A genetic lesion that arrests plasma cell homing to the bone marrow.
abstract: The coordinated regulation of chemokine responsiveness plays a critical role in the development of humoral immunity. After antigen challenge and B cell activation, the emerging plasma cells (PCs) undergo CXCL12-induced chemotaxis to the bone marrow, where they produce Ab and persist. Here we show that PCs, but not B cells or T cells from lupus-prone NZM mice, are deficient in CXCL12-induced migration. PC unresponsiveness to CXCL12 results in a marked accumulation of PCs in the spleen of mice, and a concordant decrease in bone marrow PCs. Unlike normal mice, in NZM mice, a majority of the splenic PCs are long-lived. This deficiency is a consequence of the genetic interactions of multiple systemic lupus erythematosus susceptibility loci.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
authors.forename: Loren D
authors.initials: LD
authors.lastname: Erickson
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Lin
authors.forename: Biyan
authors.initials: B
authors.lastname: Duan
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology* / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013154:Spleen / Q000276:immunology
chemical_list: D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016201:Receptors, Lymphocyte Homing