title: Mechanisms of peritoneal B-1a cells accumulation induced by murine lupus susceptibility locus Sle2.
abstract: The abundance of B-1a cells found in the peritoneal cavity of mice is under genetic control. The lupus-prone mouse New Zealand Black and New Zealand White (NZB x NZW)F(1) and its derivative NZM2410 are among the strains with the highest numbers of peritoneal B1-a cells. We have previously identified an NZM2410 genetic locus, Sle2, which is associated with the production of large numbers of B-1a cells. In this paper, we examined the mechanisms responsible for this phenotype by comparing congenic C57BL/6 mice with or without Sle2. Fetal livers generated more B-1a cells in B6.Sle2 mice, providing them with a greater starting number of B-1a cells early in life. Sle2-expressing B1-a cells proliferated significantly more in vivo than their B6 counterparts, and reciprocal adoptive transfers showed that this phenotype is intrinsic to Sle2 peritoneal B cells. The rate of apoptosis detected was significantly lower in B6.Sle2 peritoneal cavity B-1a cells than in B6, with or without exogenous B cell receptor cross-linking. Increased proliferation and decreased apoptosis did not affect Sle2 peritoneal B-2 cells. In addition, a significant number of peritoneal cavity B-1a cells were recovered in lethally irradiated B6.Sle2 mice reconstituted with B6.Igh(a) bone marrow, showing radiation resistance in Sle2 B-1a cells or its precursors. Finally, B6.Sle2 adult bone marrow and spleen were a significant source of peritoneal B-1a cells when transferred into B6.Rag2(-/-) mice. This suggests that peritoneal B-1a cells are replenished throughout the animal life span in B6.Sle2 mice. These results show that Sle2 regulates the size of the B-1a cell compartment at multiple developmental checkpoints.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, 1600 Archer Road, Gainesville, FL 32610, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Butfiloski
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Laurence
authors.initials: L
authors.lastname: Morel
mesh_terms: D019264:Adoptive Transfer; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D018956:CD5 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics* / Q000276:immunology*; D049109:Cell Proliferation; D048429:Cell Size; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D005819:Genetic Markers / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010529:Peritoneal Cavity / Q000166:cytology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D018956:CD5 Antigens; D005819:Genetic Markers