title: Identification of anergic B cells within a wild-type repertoire.
abstract: The contribution of anergy to silencing of autoreactive B cells in physiologic settings is unknown. By comparing anergic and nonanergic immunoglobulin-transgenic mouse strains, we defined a set of surface markers that were used for presumptive identification of an anergic B cell cohort within a normal repertoire. Like anergic transgenic B cells, these physiologic anergic cells exhibited high basal intracellular free calcium and did not mobilize calcium, initiate tyrosine phosphorylation, proliferate, upregulate activation markers, or mount an immune response upon antigen-receptor stimulation. Autoreactive B cells were overrepresented in this cohort. On the basis of the frequency and lifespan of these cells, it appears that as many as 50% of newly produced B cells are destined to become anergic. In conclusion, our findings indicate that anergy is probably the primary mechanism by which autoreactive B cells are silenced. Thus maintenance of the unresponsiveness of anergic cells is critical for prevention of autoimmunity.
authors.affiliation: Integrated Department of Immunology, University of Colorado Health Sciences Center and National Jewish Medical Research Center, Denver, Colorado 80206, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Merrell
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Benschop
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gauld
authors.forename: Katja
authors.initials: K
authors.lastname: Aviszus
authors.forename: Debora
authors.initials: D
authors.lastname: Decote-Ricardo
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wysocki
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
mesh_terms: D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D017635:Clonal Anergy / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017455:Receptors, IgE; C032402:complement 1q receptor