title: A novel mechanism for B cell repertoire maturation based on response by B cell precursors to pre-B receptor assembly.
abstract: The expression of different sets of immunoglobulin specificities by fetal and adult B lymphocytes is a long-standing puzzle in immunology. Recently it has become clear that production of immunoglobulin mu heavy chain and subsequent assembly with a surrogate light chain to form the pre-B cell receptor complex is critical for development of B cells. Here we show that instead of promoting pre-B cell progression as in adult bone marrow, this complex inhibits pre-B cell growth in fetal liver. Curiously, we identify a fetal-associated VH11 mu heavy chain that allows continued pre-B proliferation in fetal liver. Interestingly, this heavy chain does not associate efficiently with a surrogate light chain, providing a previously unrecognized mechanism for skewing the expression of distinctive VH genes toward fetal through early neonatal life.
authors.affiliation: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wasserman
authors.forename: Y S
authors.initials: YS
authors.lastname: Li
authors.forename: S A
authors.initials: SA
authors.lastname: Shinton
authors.forename: C E
authors.initials: CE
authors.lastname: Carmack
authors.forename: T
authors.initials: T
authors.lastname: Manser
authors.forename: D L
authors.initials: DL
authors.lastname: Wiest
authors.forename: K
authors.initials: K
authors.lastname: Hayakawa
authors.forename: R R
authors.initials: RR
authors.lastname: Hardy
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011233:Precipitin Tests; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
chemical_list: D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell