title: Definition of a novel cellular constituent of the bone marrow that regulates the response of immature B cells to B cell antigen receptor engagement.
abstract: Previously we defined a Thy1(dull) bone marrow-derived cell population that regulated fate decisions by immature B cells after Ag receptor signaling. The microenvironmental signals provided by this cell population were shown to redirect the B cell Ag receptor -induced apoptotic response of immature B cells toward continued recombination-activating gene (RAG) expression and secondary light chain recombination (receptor editing). Neither the identity of the cell responsible for this activity nor its role in immature B cell development in vivo were addressed by these previous studies. Here we show that this protective microenvironmental niche is defined by the presence of a novel Thy1(dull), DX5(pos) cell that can be found in close association with immature B cells in vivo. Depletion of this cell eliminates the anti-apoptotic effect of bone marrow in vitro and leads to a significant decrease in the number and frequency of bone marrow immature B cells in vivo. We propose that, just as the bone marrow environment is essential for the survival and progression of pro-B and pre-B cells through their respective developmental checkpoints, this cellular niche regulates the progression of immature stage B cells through negative selection.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Sandel
authors.forename: M
authors.initials: M
authors.lastname: Gendelman
authors.forename: G
authors.initials: G
authors.lastname: Kelsoe
authors.forename: J G
authors.initials: JG
authors.lastname: Monroe
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000096:biosynthesis / Q000276:immunology; D007106:Immune Sera / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000096:biosynthesis
chemical_list: D015415:Biomarkers; D007106:Immune Sera; D011947:Receptors, Antigen, B-Cell; D018800:Thy-1 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside