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• W2004366410 endingPage "1148" @default.
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• W2004366410 abstract "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.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.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." @default.
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• W2004366410 date "1995-10-01" @default.
• W2004366410 modified "2023-10-12" @default.
• W2004366410 title "Pre-B-cell development in the absence of λ5 in transgenic mice expressing a heavy-chain disease protein" @default.
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• W2004366410 doi "https://doi.org/10.1016/s0960-9822(95)00230-2" @default.
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