PMID- 21508409
OWN - NLM
STAT- MEDLINE
DCOM- 20110920
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 117
IP  - 26
DP  - 2011 Jun 30
TI  - B-cell receptors and heavy chain diseases: guilty by association?
PG  - 6991-8
LID - 10.1182/blood-2011-02-336164 [doi]
AB  - Heavy chain diseases (HCDs) are B-cell proliferative disorders characterized by 
      the production of monoclonal, incomplete, immunoglobulin (Ig) heavy chains (HCs) 
      without associated light chains (LCs). These abnormal HCs are produced as a 
      consequence of HC gene alterations in the neoplastic B cells. HC gene alterations 
      will also impact on surface HC, which is part of the B-cell receptor (BCR), a 
      crucial player in lymphocyte activation by antigen. The selective advantage 
      conferred to mutant cells by abnormal BCR without an antigen-binding domain may 
      be explained by activation of ligand-independent signaling, in analogy to what 
      has been shown for mutated oncogenic growth factor receptors. Here we review data 
      obtained from mouse models showing abnormal, constitutive activity of HCD-BCR, 
      and we discuss the possible mechanism involved, namely, aberrant spontaneous 
      self-aggregation. This self-aggregation might occur as a consequence of escape 
      from the chaperone immunoglobulin binding protein (BiP) and from the 
      anti-aggregation effect of LC association. The concept of misfolding-induced 
      signaling elaborated here may extend to other pathologies termed conformational 
      diseases.
FAU - Corcos, Daniel
AU  - Corcos D
AD  - Inserm Unite 955, Faculte de Medecine-Paris 12, Creteil, France. 
      daniel.corcos@inserm.fr
FAU - Osborn, Michael J
AU  - Osborn MJ
FAU - Matheson, Louise S
AU  - Matheson LS
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110420
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Molecular Chaperones)
RN  - 0 (Receptors, Antigen, B-Cell)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Genes, Neoplasm
MH  - Heavy Chain Disease/*genetics/metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Chaperones/metabolism
MH  - Mutation
MH  - Receptors, Antigen, B-Cell/genetics/*metabolism
MH  - Signal Transduction
EDAT- 2011/04/22 06:00
MHDA- 2011/09/21 06:00
CRDT- 2011/04/22 06:00
PHST- 2011/04/22 06:00 [entrez]
PHST- 2011/04/22 06:00 [pubmed]
PHST- 2011/09/21 06:00 [medline]
AID - S0006-4971(20)44838-4 [pii]
AID - 10.1182/blood-2011-02-336164 [doi]
PST - ppublish
SO  - Blood. 2011 Jun 30;117(26):6991-8. doi: 10.1182/blood-2011-02-336164. Epub 2011 
      Apr 20.