title: Gamma 2b provides only some of the signals normally given via mu in B cell development.
abstract: B cell development is a complex process involving interactions between B cell precursors, stroma, and known and unknown ligands and cytokines. In order to more fully understand the requirements for Ig in that development we have created transgenic mice that carry a gamma 2b transgene and express it early in B cell development. Previously it was believed that these B cells arrested in their development prior to the pro- to pre-B cell transition. We show here that in conventional gamma 2b mice, B cell development actually arrests later, at the pre-B cell stage. This shows for the first time that a constant region different from mu can allow signaling through the pre-B cell receptor, but cannot promote complete development. The pro- and pre-B cells in the conventional gamma 2b transgenics are not fully functional since they cannot grow in IL-7 without stromal cells. This is a novel phenotype, separating development from stroma independence. The few, mature B cells that do develop in these mice express both mu and gamma 2b simultaneously, and are CD5+. Expression of a Bcl-2 transgene allows survival of gamma 2b transgenic immature B cells, but does not promote full maturation, indicating that normally mu provides both an anti-apoptotic signal and a differentiation signal. One line of gamma 2b mice, the C line, does not have this phenotype. B cell development is accelerated in this unconventional line, and the developing B cells have a very different phenotype from both normal mice and conventional gamma 2b mouse lines, but are very similar to mu transgenics. Mature B cells are largely CD5-, gamma 2b-only expressing. This unique phenotype is apparently due to the activation in B cell precursors of a gene at the insertion site of the transgene, circumventing the need for mu. Comparison of conventional gamma 2b transgenics with the C line and mu transgenics reveals the multiple signals required throughout B cell development.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Kurtz
authors.forename: P L
authors.initials: PL
authors.lastname: Witte
authors.forename: U
authors.initials: U
authors.lastname: Storb
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006410:Hematopoiesis / Q000502:physiology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000502:physiology; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000502:physiology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000473:pathology; D016130:Immunophenotyping; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000473:pathology
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D019253:Proto-Oncogene Proteins c-bcl-2