B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D mu protein and selection of DH element reading frames

Cell. 1991 Apr 5;65(1):47-54. doi: 10.1016/0092-8674(91)90406-o.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens / immunology
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Biological Evolution
  • Cell Differentiation / genetics
  • Codon
  • DNA
  • Exons
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Open Reading Frames
  • Protein Biosynthesis
  • Sequence Homology, Nucleic Acid
  • Signal Transduction


  • Antigens
  • Codon
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Membrane Proteins
  • DNA

Associated data

  • GENBANK/M60955
  • GENBANK/M60956
  • GENBANK/M60957
  • GENBANK/M60958
  • GENBANK/M60959
  • GENBANK/M60960
  • GENBANK/M60961
  • GENBANK/M60962
  • GENBANK/M64383
  • GENBANK/M64384