A role for the IgH intronic enhancer E mu in enforcing allelic exclusion.
The intronic enhancer (E mu) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine E mu's subsequent functions, we created an Igh allele with assembled V(H) gene but with E mu removed. In mice homozygous for this E mu-deficient allele, B cell development was normal and indistinguishable from that of mice with the same V(H) knockin and E mu intact. In mice heterozygous for the E mu-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for E mu in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.
Li
Fubin
F
Hunter College and Graduate Center of the City University of New York, New York, NY 10065, USA.
Eckhardt
Laurel A
LA
D000483:Alleles; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D052058:Hinge Exons / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007072:Immunoglobulin D / Q000032:analysis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000032:analysis / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000032:analysis / Q000235:genetics; D013154:Spleen / Q000166:cytology; D050441:VDJ Exons / Q000235:genetics
D018398:Homeodomain Proteins; D007072:Immunoglobulin D; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; C064658:RAG-1 protein