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

H Gu, D Kitamura, K Rajewsky - Cell, 1991 - cell.com
H Gu, D Kitamura, K Rajewsky
Cell, 1991cell.com
In productively rearranged murine V.-D.-J. genes (encoding immunoglobulin heavy chain
variable regions), the D. elements are preferentially used in one particular reading frame
(RF1), although the recombination breakpoints at the O.-J. 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 D.-J. rearrangement: RF3 is counterselected on the
basis of stop codons. RF2 allows the expression of a truncated~ chain (DI~ protein) from …
Summary
In productively rearranged murine V.-D.-J. genes (encoding immunoglobulin heavy chain variable regions), the D. elements are preferentially used in one particular reading frame (RF1), although the recombination breakpoints at the O.-J. 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 D.-J. rearrangement: RF3 is counterselected on the basis of stop codons. RF2 allows the expression of a truncated~ chain (DI~ protein) from most D.-J. joints. Using B cells in which the membrane exon of the I1 chain is disrupted by homologous recombination on one of the two homologous chromosomes, we obtain evidence that membranebound DI~ signals arrest of differentiation, presumably by preventing V.-DJ joining. In addition to RF3 and RF2 counterselection, promotion of D.-J. joining in areas of sequence homology further enforces RF1 usage.
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