title: Essential role for CAML in follicular B cell survival and homeostasis.
abstract: Calcium-modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein that is important during thymopoiesis. However, whether it serves a function in mature lymphocytes is unknown. In this article, we show that CAML is essential for survival of peripheral follicular (Fo) B cells. Conditional deletion of CAML in CD19-Cre transgenic mice caused a significant reduction in Fo cell numbers and increased rates of homeostatic proliferation. CAML-deficient Fo cells showed increased cellular turnover and normal proliferative ability. Although CAML-deficient Fo cells responded to AgR stimulation and to B cell activating factor, they displayed decreased survival and increased apoptosis following stimulation with LPS and IL-4 in vitro. Failure to survive was not due to aberrant B cell development in the absence of CAML, because induced deletion of the gene in mature cells resulted in a similar phenotype. These data establish an essential and ongoing role for CAML in the long-term survival of mature B cells.
authors.affiliation: Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Zane
authors.forename: Justin H
authors.initials: JH
authors.lastname: Gundelach
authors.forename: Lonn D
authors.initials: LD
authors.lastname: Lindquist
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bram
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053264:B-Cell Activating Factor / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002470:Cell Survival; D006706:Homeostasis; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053264:B-Cell Activating Factor; C490314:Caml protein, mouse; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4