title: Antinuclear antigen B cells that down-regulate surface B cell receptor during development to mature, follicular phenotype do not display features of anergy in vitro.
abstract: We previously demonstrated that B cells expressing a transgenic BCR with "dual reactivity" for the hapten arsonate and nuclear autoantigens efficiently complete development to follicular phenotype and stably reside in follicles in vivo. These B cells express very low levels of surface IgM and IgD, suggesting that they avoid central deletion and peripheral anergy by reducing their avidity for autoantigen via surface BCR (sBCR) down-regulation. Since a variety of states of B cell anergy have been previously described, a thorough examination of the functional capabilities of these B cells was required to test this hypothesis. In this study, we show that surface Ig cross-linking induces amounts of proximal BCR signaling in these B cells commensurate with their reduced sBCR levels. Functionally, however, they are comparable to nonautoreactive B cells in cell cycle progression, up-regulation of activation and costimulatory molecules, and Ab-forming cell differentiation when treated with a variety of stimuli in vitro. In addition, these B cells can efficiently process and present Ag and are capable of undergoing cognate interaction with naive TCR-transgenic T cells, resulting in robust IL-2 production. Together, these data reveal a lack of intrinsic anergy involving any known mechanism, supporting the idea that this type of antinuclear Ag B cell becomes indifferent to cognate autoantigen by down-regulating sBCR.
authors.affiliation: Department of Microbiology and Immunology and Kimmel Cancer Center, Jefferson Medical College, Philadelphia, PA 19017-5541, USA.
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Liu
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology; D017951:Antigen Presentation; D001324:Autoantigens / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002453:Cell Cycle; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000276:immunology; D017635:Clonal Anergy; D015536:Down-Regulation; D006825:Hybridomas / Q000276:immunology; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell