PMID- 15114669
OWN - NLM
STAT- MEDLINE
DCOM- 20040629
LR  - 20071114
IS  - 0014-2980 (Print)
IS  - 0014-2980 (Linking)
VI  - 34
IP  - 5
DP  - 2004 May
TI  - Chronic graft-versus-host reaction is associated with a decrease in Ig light 
      chain receptor editing in bone marrow self-reactive B cells.
PG  - 1361-70
AB  - The encounter of developing B cells in the bone marrow with soluble hen egg 
      lysozyme (sHEL) self antigen induces anergy and endogenous kappa light chain 
      rearrangements ('receptor editing'). We have previously shown that induction of 
      chronic graft-versus-host reaction (GVH) in tolerant Ig/sHEL mice results in 
      prevention of B cell anergy in the bone marrow and the spleen. We now report that 
      in chronic GVH, immature self-reactive B cells also show reduced levels of 
      receptor editing in the bone marrow. This is evidenced by the following 
      observations: (a) a small population of'receptor-edited' B cells, which is found 
      in tolerant mice, is markedly reduced in mice that have lost tolerance in chronic 
      GVH; (b) self-reactive B cells in GVH mice have reduced levels of endogenous 
      kappa chain rearrangements; and (c) recombinase-activating gene (RAG)-2 
      expression is markedly decreased in immature self-reactive B cells in the bone 
      marrow of chronic GVH mice. These results suggest that in chronic GVH newly 
      emerging B cells escape tolerance, in part because of decreased receptor editing 
      in the bone marrow. Thus, the autoimmunity induced by chronic GVH may ultimately 
      result from the failure of B cell tolerance at multiple checkpoints.
FAU - Feuerstein, Nili
AU  - Feuerstein N
AD  - Division of Rheumatology, The Children's Hospital of Philadelphia, University of 
      Pennsylvania, Philadelphia, 19104, USA. feuerstein@email.chop.edu
FAU - DeSimone, Dennis C
AU  - DeSimone DC
FAU - Eisenberg, Robert A
AU  - Eisenberg RA
FAU - Finkel, Terri H
AU  - Finkel TH
LA  - eng
GR  - R01 AI30575/AI/NIAID NIH HHS/United States
GR  - R01 AI34156/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Rag2 protein, mouse)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - 0 (V(D)J recombination activating protein 2)
SB  - IM
MH  - Animals
MH  - Autoimmunity/*immunology
MH  - B-Lymphocytes/*immunology
MH  - Chronic Disease
MH  - DNA-Binding Proteins/biosynthesis/genetics
MH  - Graft vs Host Disease/*immunology
MH  - Immunoglobulin Light Chains/immunology
MH  - Mice
MH  - Receptors, Antigen, B-Cell/*immunology
EDAT- 2004/04/29 05:00
MHDA- 2004/06/30 05:00
CRDT- 2004/04/29 05:00
PHST- 2004/04/29 05:00 [pubmed]
PHST- 2004/06/30 05:00 [medline]
PHST- 2004/04/29 05:00 [entrez]
AID - 10.1002/eji.200324743 [doi]
PST - ppublish
SO  - Eur J Immunol. 2004 May;34(5):1361-70. doi: 10.1002/eji.200324743.