Expression of a V region-less B cell receptor confers a tolerance-like phenotype on transgenic B cells.
Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellular domain. It has been speculated that deletion of the Ag binding domain would confer a constitutive activity on the BCR, as it has been shown for oncogenic growth factor receptors. A V region-less BCR has constitutive activity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in pre-B cell development. However, it has been speculated that normal Ag receptors also display constitutive activity. Here we show that transgenic B cells expressing a membrane H chain disease protein on their surface are phenotypically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are eliminated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors develop as mature B cells. These findings support the view that the truncated BCR has a constitutive activity that mimics ligand binding, in analogy to what has been shown for oncogenic growth factor receptors.
Corcos
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Institut Cochin de Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale Unité 257, Paris, France. corcos@cochin.inserm.fr
Grandien
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Vazquez
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A
Dunda
O
O
Lorès
P
P
Bucchini
D
D
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D003433:Crosses, Genetic; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes / Q000276:immunology*
D007147:Immunoglobulin Light Chains; D007148:Immunoglobulin mu-Chains; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell