The C(H)1 and transmembrane domains of mu in the context of a gamma2b transgene do not suffice to promote B cell maturation.
Mice carrying a gamma2b transgene have been shown previously to be deficient in B cell development. In particular, a developmental block exists at the pre-B cell stage. The few B cells that develop all express endogenous micro heavy chains. The phenotype suggests that gamma2b exerts a strong feedback inhibition on endogenous Ig gene rearrangement, but, unlike micro, cannot support further B cell development. In this study we have created hybrid transgenes between gamma2b and micro. Transgenic mice with a C(H)1 domain of micro, or both a C(H)1 and transmembrane/cytoplasmic domain of micro replacing the respective domains of a gamma2b transgene, have the same B cell defect as gamma2b transgenic mice. Interestingly, the severity of the defect is correlated with the level of expression of the transgene, suggesting that the degree of feedback inhibition of Ig gene rearrangement depends on the level and timing of Ig production. Crossing the gamma2b/micro transgenes into a Bcl-x(L) transgenic line allows immature gamma2b B cells to survive, but not to develop to maturity. Therefore, the missing function of micro is not simply an anti-apoptotic effect.
Shen
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X
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
Bozek
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G
Pinkert
C A
CA
Storb
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U
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015139:Blotting, Southern; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D005434:Flow Cytometry; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000502:physiology*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012313:RNA / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D012313:RNA