PMID- 26773143
OWN - NLM
STAT- MEDLINE
DCOM- 20160616
LR  - 20160206
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 196
IP  - 4
DP  - 2016 Feb 15
TI  - Fatty Acid Amide Hydrolase Regulates Peripheral B Cell Receptor Revision,
      Polyreactivity, and B1 Cells in Lupus.
PG  - 1507-16
LID - 10.4049/jimmunol.1500291 [doi]
AB  - C57BL/6 mice bearing the Sle2(z) lupus-susceptibility congenic interval on
      chromosome 4 display high titers of polyclonal autoantibodies with generalized B 
      cell hyperactivity, hallmarks of systemic lupus erythematosus. In
      B6.Sle2(z)HEL(Ig).sHEL BCR-transgenic mice, Sle2(z) did not breach central
      tolerance, but it led to heightened expression of endogenous Ig H and L chains in
      splenic B cells, upregulation of RAG, and serological polyreactivity, suggestive 
      of excessive receptor revision. Fatty acid amide hydrolase (FAAH), a gene in the 
      minimal subcongenic interval generated through recombinant mapping, was found to 
      be upregulated in Sle2(z) B cells by microarray analysis, Western blot, and
      functional assays. Pharmacological inhibition of FAAH reversed the increase in
      receptor revision, RAG expression, and polyreactive autoantibodies in lupus-prone
      mice. These studies indicate that increased peripheral BCR revision, or selective
      peripheral expansion of BCR-revised B cells, may lead to systemic autoimmunity
      and that FAAH is a lupus-susceptibility gene that might regulate this process.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Pathak, Simanta
AU  - Pathak S
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390; Department of Biomedical
      Engineering, University of Houston, Houston, TX 77204;
FAU - Kumar, Kirthi Raman
AU  - Kumar KR
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390;
FAU - Kanta, Hasna
AU  - Kanta H
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390;
FAU - Carr-Johnson, Ferdicia
AU  - Carr-Johnson F
AD  - Center for Immunology, University of Texas Southwestern Medical Center, Dallas,
      TX 75390; and.
FAU - Han, Jie
AU  - Han J
AUID- ORCID: http://orcid.org/0000-0002-6553-7197
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390;
FAU - Bashmakov, Anna
AU  - Bashmakov A
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390;
FAU - Faure, Lionel
AU  - Faure L
AD  - Center for Plant Lipid Research, University of North Texas, Denton, TX 76203.
FAU - Ding, Huihua
AU  - Ding H
AUID- ORCID: http://orcid.org/0000-0002-7530-8953
AD  - Department of Biomedical Engineering, University of Houston, Houston, TX 77204;
FAU - Vanarsa, Kamala
AU  - Vanarsa K
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390; Department of Biomedical
      Engineering, University of Houston, Houston, TX 77204;
FAU - Khan, Shaheen
AU  - Khan S
AUID- ORCID: http://orcid.org/0000-0002-1472-8129
AD  - Center for Immunology, University of Texas Southwestern Medical Center, Dallas,
      TX 75390; and.
FAU - Li, Quan-Zhen
AU  - Li QZ
AUID- ORCID: http://orcid.org/0000-0002-7257-0489
AD  - Center for Immunology, University of Texas Southwestern Medical Center, Dallas,
      TX 75390; and.
FAU - Chapman, Kent
AU  - Chapman K
AUID- ORCID: http://orcid.org/0000-0003-0489-3072
AD  - Center for Plant Lipid Research, University of North Texas, Denton, TX 76203.
FAU - Wakeland, Edward K
AU  - Wakeland EK
AUID- ORCID: http://orcid.org/0000-0002-7107-0992
AD  - Center for Immunology, University of Texas Southwestern Medical Center, Dallas,
      TX 75390; and.
FAU - Mohan, Chandra
AU  - Mohan C
AD  - Division of Rheumatic Diseases, Department of Internal Medicine, University of
      Texas Southwestern Medical Center, Dallas, TX 75390; Department of Biomedical
      Engineering, University of Houston, Houston, TX 77204; Center for Immunology,
      University of Texas Southwestern Medical Center, Dallas, TX 75390; and
      texascmohan@gmail.com.
LA  - eng
GR  - AR055600/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20160115
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Autoantibodies)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.1.- (fatty-acid amide hydrolase)
SB  - AIM
SB  - IM
MH  - Amidohydrolases/genetics/*metabolism
MH  - Animals
MH  - Autoantibodies/immunology
MH  - B-Lymphocyte Subsets/*immunology
MH  - B-Lymphocytes/immunology/physiology
MH  - Genetic Predisposition to Disease
MH  - Immune Tolerance/genetics
MH  - Lupus Erythematosus, Systemic/genetics/*immunology
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microarray Analysis
MH  - Receptors, Antigen, B-Cell/*immunology/metabolism
MH  - Spleen/cytology/immunology
EDAT- 2016/01/17 06:00
MHDA- 2016/06/17 06:00
CRDT- 2016/01/17 06:00
PHST- 2015/02/06 00:00 [received]
PHST- 2015/12/07 00:00 [accepted]
PHST- 2016/01/17 06:00 [entrez]
PHST- 2016/01/17 06:00 [pubmed]
PHST- 2016/06/17 06:00 [medline]
AID - jimmunol.1500291 [pii]
AID - 10.4049/jimmunol.1500291 [doi]
PST - ppublish
SO  - J Immunol. 2016 Feb 15;196(4):1507-16. doi: 10.4049/jimmunol.1500291. Epub 2016
      Jan 15.