PMID- 20661465
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 7
DP  - 2010 Jul 21
TI  - B cell activating factor (BAFF) and T cells cooperate to breach B cell tolerance 
      in lupus-prone New Zealand Black (NZB) mice.
PG  - e11691
LID - 10.1371/journal.pone.0011691 [doi]
LID - e11691
AB  - The presence of autoantibodies in New Zealand Black (NZB) mice suggests a B cell 
      tolerance defect however the nature of this defect is unknown. To determine 
      whether defects in B cell anergy contribute to the autoimmune phenotype in NZB 
      mice, soluble hen egg lysozyme (sHEL) and anti-HEL Ig transgenes were bred onto 
      the NZB background to generate double transgenic (dTg) mice. NZB dTg mice had 
      elevated levels of anti-HEL antibodies, despite apparently normal B cell 
      functional anergy in-vitro. NZB dTg B cells also demonstrated increased survival 
      and abnormal entry into the follicular compartment following transfer into sHEL 
      mice. Since this process is dependent on BAFF, BAFF serum and mRNA levels were 
      assessed and were found to be significantly elevated in NZB dTg mice. Treatment 
      of NZB sHEL recipient mice with TACI-Ig reduced NZB dTg B cell survival following 
      adoptive transfer, confirming the role of BAFF in this process. Although NZB mice 
      had modestly elevated BAFF, the enhanced NZB B cell survival response appeared to 
      result from an altered response to BAFF. In contrast, T cell blockade had a 
      minimal effect on B cell survival, but inhibited anti-HEL antibody production. 
      The findings suggest that the modest BAFF elevations in NZB mice are sufficient 
      to perturb B cell tolerance, particularly when acting in concert with B cell 
      functional abnormalities and T cell help.
FAU - Chang, Nan-Hua
AU  - Chang NH
AD  - Arthritis Centre of Excellence, Toronto Western Research Institute, Toronto, 
      Ontario, Canada.
FAU - Cheung, Yui-Ho
AU  - Cheung YH
FAU - Loh, Christina
AU  - Loh C
FAU - Pau, Evelyn
AU  - Pau E
FAU - Roy, Valerie
AU  - Roy V
FAU - Cai, Yong-Chun
AU  - Cai YC
FAU - Wither, Joan
AU  - Wither J
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100721
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Autoantibodies)
RN  - 0 (B-Cell Activating Factor)
RN  - EC 3.2.1.- (hen egg lysozyme)
RN  - EC 3.2.1.17 (Muramidase)
SB  - IM
MH  - Animals
MH  - Autoantibodies/immunology
MH  - B-Cell Activating Factor/*blood/*immunology
MH  - B-Lymphocytes/*immunology/metabolism
MH  - Immune Tolerance/genetics/immunology
MH  - Lupus Erythematosus, Systemic/genetics/*immunology
MH  - Mice
MH  - Mice, Transgenic
MH  - Muramidase/genetics/physiology
MH  - T-Lymphocytes/*immunology/metabolism
PMC - PMC2908288
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/07/28 06:00
MHDA- 2010/10/29 06:00
PMCR- 2010/07/21
CRDT- 2010/07/28 06:00
PHST- 2010/03/08 00:00 [received]
PHST- 2010/06/17 00:00 [accepted]
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
PHST- 2010/07/21 00:00 [pmc-release]
AID - 10-PONE-RA-16860R1 [pii]
AID - 10.1371/journal.pone.0011691 [doi]
PST - epublish
SO  - PLoS One. 2010 Jul 21;5(7):e11691. doi: 10.1371/journal.pone.0011691.