title: A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and lupus-prone mice.
abstract: OBJECTIVE
  B-1 cells have long been suggested to play an important role in lupus. However, reports to date have been controversial regarding their pathogenic or protective roles in different animal models. We undertook this study to investigate a novel subpopulation of B-1 cells and its roles in murine lupus.
  
  
  METHODS
  Lymphocyte phenotypes were assessed by flow cytometry. Autoantibody secretion was analyzed by enzyme-linked immunosorbent assay, autoantigen proteome array, and antinuclear antibody assay. Cell proliferation was measured by thymidine incorporation and 5,6-carboxyfluorescein succinimidyl ester dilution. B cell Ig isotype switching was measured by enzyme-linked immunospot assay.
  
  
  RESULTS
  Anti-double-stranded DNA (anti-dsDNA) autoantibodies were preferentially secreted by a subpopulation of CD5+ B-1 cells that expressed programmed death ligand 2 (termed L2pB1 cells). A substantial proportion of hybridoma clones generated from L2pB1 cells reacted to dsDNA. Moreover, these clones were highly cross-reactive with other lupus-related autoantigens. L2pB1 cells were potent antigen-presenting cells and promoted Th17 cell differentiation in vitro. A dramatic increase of circulating L2pB1 cells in lupus-prone BXSB mice was correlated with elevated serum titers of anti-dsDNA antibodies. A significant number of L2pB1 cells preferentially switched to IgG1 and IgG2b when stimulated with interleukin-21.
  
  
  CONCLUSIONS
  Our findings identify a novel subpopulation of B-1 cells that is enriched for autoreactive specificities, undergoes isotype switch, manifests enhanced antigen presentation, promotes Th17 cell differentiation, and is preferentially associated with the development of lupus in a murine model. Together, these findings suggest that L2pB1 cells have the potential to initiate autoimmunity through serologic and T cell-mediated mechanisms.
authors: Boston University Medical Center, Boston, Massachusetts 02118, USA. xuemei.zhong@bmc.org
authors: Xuemei
authors: X
authors: Zhong
authors: Stanley
authors: S
authors: Lau
authors: Chunyan
authors: C
authors: Bai
authors: Nicolas
authors: N
authors: Degauque
authors: Nichol E
authors: NE
authors: Holodick
authors: Scott J
authors: SJ
authors: Steven
authors: Joseph
authors: J
authors: Tumang
authors: Wenda
authors: W
authors: Gao
authors: Thomas L
authors: TL
authors: Rothstein
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000097:blood; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D018956:CD5 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D006825:Hybridomas; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000378:metabolism; D061027:Programmed Cell Death 1 Ligand 2 Protein; D000098546:Interleukin-21
chemical_list: D000974:Antibodies, Antinuclear; D018956:CD5 Antigens; D007074:Immunoglobulin G; D007378:Interleukins; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D004247:DNA; D000098546:Interleukin-21