Deletion of immunoglobulin beta in developing B cells leads to cell death.
Inducible gene-targeting experiments have shown that Igmu expression is essential for maintaining survival of mature B cells, but the role of Igmu expression in immature B cell survival has not been determined. To assess whether continued B cell receptor (BCR) expression is required for bone marrow B cell precursor development and survival, we developed a method for conditional gene deletion in these cells. Recombination-activating gene regulatory elements were used to express Igbeta cDNA as a transgene to complement Igbeta(-/-) mice. Transgenic Igbeta expression was found in proB and small preB cells and was extinguished in large preB and immature B cells. Igbeta deletion from large preB cells and immature B cells resulted in cell death that could be rescued by transgenic bcl-2 expression. However, transgenic bcl-2 expression was unable to restore B cell development in the absence of Igbeta. We conclude that Igbeta expression is essential to maintain preB cell and immature B cell survival and to mediate B cell differentiation. In addition, complementation of null mutations with cDNAs under the control of heterologous bacterial artificial chromosomes is a useful method for cell-type-specific and developmentally regulated gene ablation in vivo.
Meffre
Eric
E
Laboratory of Molecular Immunology, The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021-6399, USA.
Nussenzweig
Michel C
MC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D016923:Cell Death; D002470:Cell Survival; D022202:Chromosomes, Artificial, Bacterial; D017353:Gene Deletion; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology
D007136:Immunoglobulins; C038767:immunoglobulin B