B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D mu protein and selection of DH element reading frames.
In productively rearranged murine VH-DH-JH genes (encoding immunoglobulin heavy chain variable regions), the DH elements are preferentially used in one particular reading frame (RF1), although the recombination breakpoints at the DH-JH border vary. Despite this variability, the bias of RF usage is not due to cellular selection by antigen but is quantitatively established at the stage of DH-JH rearrangement: RF3 is counterselected on the basis of stop codons. RF2 allows the expression of a truncated mu chain (D mu protein) from most DH-JH joints. Using B cells in which the membrane exon of the mu chain is disrupted by homologous recombination on one of the two homologous chromosomes, we obtain evidence that membrane-bound D mu signals arrest of differentiation, presumably by preventing VH-DHJH joining. In addition to RF3 and RF2 counterselection, promotion of DH-JH joining in areas of sequence homology further enforces RF1 usage.
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Institute for Genetics University of Cologne Federal Republic of Germany.
Kitamura
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Rajewsky
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D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001483:Base Sequence; D005075:Biological Evolution; D002454:Cell Differentiation / Q000235:genetics; D003062:Codon; D004247:DNA; D005091:Exons; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction
D000941:Antigens; D003062:Codon; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D008565:Membrane Proteins; D004247:DNA