PMID- 19950285
OWN - NLM
STAT- MEDLINE
DCOM- 20100218
LR  - 20211020
IS  - 0004-3591 (Print)
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 60
IP  - 12
DP  - 2009 Dec
TI  - A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and 
      lupus-prone mice.
PG  - 3734-43
LID - 10.1002/art.25015 [doi]
AB  - 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. CONCLUSION: 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.
FAU - Zhong, Xuemei
AU  - Zhong X
AD  - Boston University Medical Center, Boston, Massachusetts 02118, USA. 
      xuemei.zhong@bmc.org
FAU - Lau, Stanley
AU  - Lau S
FAU - Bai, Chunyan
AU  - Bai C
FAU - Degauque, Nicolas
AU  - Degauque N
FAU - Holodick, Nichol E
AU  - Holodick NE
FAU - Steven, Scott J
AU  - Steven SJ
FAU - Tumang, Joseph
AU  - Tumang J
FAU - Gao, Wenda
AU  - Gao W
FAU - Rothstein, Thomas L
AU  - Rothstein TL
LA  - eng
GR  - R01 AI029690-09/AI/NIAID NIH HHS/United States
GR  - AI-029690/AI/NIAID NIH HHS/United States
GR  - R56 AI029690/AI/NIAID NIH HHS/United States
GR  - R01 AI029690/AI/NIAID NIH HHS/United States
GR  - P01 AI060896/AI/NIAID NIH HHS/United States
GR  - P01 AI060896-06/AI/NIAID NIH HHS/United States
GR  - AI-060896/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Antibodies, Antinuclear)
RN  - 0 (CD5 Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukins)
RN  - 0 (Pdcd1lg2 protein, mouse)
RN  - 0 (Peptides)
RN  - 0 (Programmed Cell Death 1 Ligand 2 Protein)
RN  - 9007-49-2 (DNA)
RN  - MKM3CA6LT1 (interleukin-21)
SB  - IM
MH  - Animals
MH  - Antibodies, Antinuclear/*biosynthesis/blood
MH  - Autoimmunity/*immunology
MH  - B-Lymphocytes/*metabolism
MH  - CD5 Antigens/metabolism
MH  - Cell Proliferation
MH  - DNA/immunology
MH  - Disease Models, Animal
MH  - Hybridomas
MH  - Immunoglobulin Class Switching
MH  - Immunoglobulin G/immunology
MH  - Interleukins/pharmacology
MH  - Lupus Erythematosus, Systemic/blood/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Peptides/metabolism
MH  - Programmed Cell Death 1 Ligand 2 Protein
PMC - PMC2868318
MID - NIHMS196159
EDAT- 2009/12/02 06:00
MHDA- 2010/02/19 06:00
PMCR- 2010/05/12
CRDT- 2009/12/02 06:00
PHST- 2009/12/02 06:00 [entrez]
PHST- 2009/12/02 06:00 [pubmed]
PHST- 2010/02/19 06:00 [medline]
PHST- 2010/05/12 00:00 [pmc-release]
AID - 10.1002/art.25015 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2009 Dec;60(12):3734-43. doi: 10.1002/art.25015.