PMID- 8548286
OWN - NLM
STAT- MEDLINE
DCOM- 19960222
LR  - 20190728
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 5
IP  - 10
DP  - 1995 Oct 1
TI  - Pre-B-cell development in the absence of lambda 5 in transgenic mice expressing a 
      heavy-chain disease protein.
PG  - 1140-8
AB  - BACKGROUND: Heavy-chain diseases (HCDs) are human lymphoproliferative neoplasias 
      that are characterized by the secretion of truncated immunoglobulin heavy chains 
      devoid of light chains. We have previously proposed--by analogy to the process by 
      which mutated growth factor receptors can be oncogenic--that because the genetic 
      defects in HCDs result in the production of abnormal membrane-associated heavy 
      chains lacking an antigen-binding domain, these abnormal B-cell antigen receptors 
      might engage in ligand-independent signalling. Normal pre-B-cell development 
      requires the presence of the pre-B-cell receptor, formed by the association of mu 
      heavy chains with two polypeptides--so-called surrogate light chains, Vpre-B and 
      lambda 5--that are homologous to the variable and constant portions of 
      immunoglobulin light chains, respectively. To assess whether amino-terminal 
      truncation of membrane-associated heavy chains results in their constitutive 
      activation, we have examined the ability of a HCD-associated mu protein to 
      promote pre-B-cell development in transgenic mice. RESULTS: When the mu HCD 
      transgene is introduced into SCID mice, CD43- pre-B cells develop normally. To 
      determine whether this pre-B-cell development requires surrogate light chains, we 
      backcrossed mice expressing full-length or truncated mu transgenes with lambda 
      5-deficient mice. Our results show that the truncated heavy chain, but not the 
      normal chain, is able to promote pre-B-cell development in the absence of lambda 
      5. We also show that truncated mu chains spontaneously aggregate at the surface 
      of bone marrow cells. CONCLUSIONS: Expression of the truncated mu heavy chain 
      overrides a tightly controlled step of pre-B-cell development, which strongly 
      suggests that a constitutive signal is delivered by the truncated mu chain 
      disease protein. The self-aggregation of mu chain disease proteins might account 
      for this constitutive activation. We conclude that amino-terminal truncation of 
      heavy chains could play a role in the genesis of HCD neoplasia if it occurs at an 
      appropriate stage of B-cell differentiation, namely in a mature B cell.
FAU - Corcos, D
AU  - Corcos D
AD  - Institut Cochin de Genetique Moleculaire, Unite INSERM 257, Paris, France.
FAU - Dunda, O
AU  - Dunda O
FAU - Butor, C
AU  - Butor C
FAU - Cesbron, J Y
AU  - Cesbron JY
FAU - Lores, P
AU  - Lores P
FAU - Bucchini, D
AU  - Bucchini D
FAU - Jami, J
AU  - Jami J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Antigens, CD)
RN  - 0 (DNA Primers)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Immunoglobulin Light Chains, Surrogate)
RN  - 0 (Immunoglobulin gamma-Chains)
RN  - 0 (Immunoglobulin mu-Chains)
RN  - 0 (Leukosialin)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spn protein, mouse)
RN  - 0 (heavy chain disease proteins, human)
SB  - IM
MH  - Animals
MH  - *Antigens, CD
MH  - B-Lymphocytes/*cytology/immunology
MH  - Base Sequence
MH  - Cell Differentiation
MH  - DNA Primers
MH  - Gene Deletion
MH  - Heavy Chain Disease
MH  - Hematopoietic Stem Cells/cytology
MH  - Immunoglobulin Light Chains/genetics/*metabolism
MH  - Immunoglobulin Light Chains, Surrogate
MH  - Immunoglobulin gamma-Chains/*metabolism
MH  - Immunoglobulin mu-Chains/genetics/*metabolism
MH  - Leukosialin
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Peptide Fragments/metabolism
MH  - Sialoglycoproteins/metabolism
EDAT- 1995/10/01 00:00
MHDA- 1995/10/01 00:01
CRDT- 1995/10/01 00:00
PHST- 1995/10/01 00:00 [pubmed]
PHST- 1995/10/01 00:01 [medline]
PHST- 1995/10/01 00:00 [entrez]
AID - S0960-9822(95)00230-2 [pii]
AID - 10.1016/s0960-9822(95)00230-2 [doi]
PST - ppublish
SO  - Curr Biol. 1995 Oct 1;5(10):1140-8. doi: 10.1016/s0960-9822(95)00230-2.