title: VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but functional allelic exclusion of the IgH locus.
abstract: At the precursor B cell stage during bone marrow B cell development, Ig muH chain associates with surrogate L (SL) chain, which is encoded by the three genes VpreB1, VpreB2, and lambda 5, to form the pre-B cell receptor (pre-BCR). Surface expression of the pre-BCR is believed to signal both proliferation and allelic exclusion of the IgH locus. Mice which lack either VpreB1/VpreB2 or lambda 5 show a lack of precursor B cell expansion but normal IgH allelic exclusion. This would suggest that one of either lambda 5 or VpreB can make a pre-BCR-like complex which is still able to signal allelic exclusion but not proliferation. To investigate this, we established mice lacking all components of the SL chain. These mice showed severely impaired B cell development which was similar to that previously found in mice lacking either lambda 5 or VpreB1/VpreB2. Surprisingly, the IgH locus was still allelically excluded and thus the SL chain appears not to be involved in allelic exclusion.
authors.affiliation: Basel Institute for Immunology, Basel, Switzerland. shimizu@rs.noda.tus.ac.jp
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mundt
authors.forename: Steve
authors.initials: S
authors.lastname: Licence
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Mårtensson
mesh_terms: D000483:Alleles; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D005786:Gene Expression Regulation / Q000276:immunology; D005819:Genetic Markers / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics*; D054444:Immunoglobulin Light Chains, Surrogate; D007075:Immunoglobulin M / Q000097:blood; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010537:Peritoneum / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology
chemical_list: D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins