title: B-cell lymphopoiesis is regulated by cathepsin L.
abstract: Cathepsin L (CTSL) is a ubiquitously expressed lysosomal cysteine peptidase with diverse and highly specific functions. The involvement of CTSL in thymic CD4+ T-cell positive selection has been well documented. Using CTSL(nkt/nkt) mice that lack CTSL activity, we have previously demonstrated that the absence of CTSL activity affects the homeostasis of the T-cell pool by decreasing CD4+ cell thymic production and increasing CD8+ thymocyte production. Herein we investigated the influence of CTSL activity on the homeostasis of peripheral B-cell populations and bone marrow (BM) B-cell maturation. B-cell numbers were increased in lymph nodes (LN), spleen and blood from CTSL (nkt/nkt) mice. Increases in splenic B-cell numbers were restricted to transitional T1 and T2 cells and to the marginal zone (MZ) cell subpopulation. No alterations in the proliferative or apoptosis levels were detected in peripheral B-cell populations from CTSL (nkt/nkt) mice. In the BM, the percentage and the absolute number of pre-pro-B, pro-B, pre-B, immature and mature B cells were not altered. However, in vitro and in vivo experiments showed that BM B-cell production was markedly increased in CTSL (nkt/nkt) mice. Besides, BM B-cell emigration to the spleen was increased in CTSL (nkt/nkt) mice. Colony-forming unit pre-B (CFU pre-B) assays in the presence of BM stromal cells (SC) and reciprocal BM chimeras revealed that both BM B-cell precursors and SC would contribute to sustain the increased B-cell hematopoiesis in CTSL (nkt/nkt) mice. Overall, our data clearly demonstrate that CTSL negatively regulates BM B-cell production and output therefore influencing the homeostasis of peripheral B cells.
authors.affiliation: Laboratorio de Inmunología Experimental, Instituto de Medicina Experimental-Consejo Nacional de Investigaciones Científicas y Técnicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Maria Noel
authors.initials: MN
authors.lastname: Badano
authors.forename: Gabriela Lorena
authors.initials: GL
authors.lastname: Camicia
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lombardi
authors.forename: Andrea
authors.initials: A
authors.lastname: Maglioco
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cabrera
authors.forename: Hector
authors.initials: H
authors.lastname: Costa
authors.forename: Roberto Pablo
authors.initials: RP
authors.lastname: Meiss
authors.forename: Isabel
authors.initials: I
authors.lastname: Piazzon
authors.forename: Irene
authors.initials: I
authors.lastname: Nepomnaschy
mesh_terms: D000818:Animals; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D056668:Cathepsin L / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006706:Homeostasis; D008198:Lymph Nodes / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology
chemical_list: D056668:Cathepsin L; C534278:Ctsl protein, mouse