IMMUNOGLOBULIN GENE REARRANGEMENT DURING PRE-B CELL-DIFFERENTIATION

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 1  (1) , 31-38
Abstract
Experiments were designed to answer 2 questions: At what stage in normal pre-B cell development do Ig gene rearrangements occur?; and, Do H chain and .kappa. L chain genes rearrange in concert, or in an ordered sequence? To answer these questions, Ig gene rearrangements were studied in pre-B cell [mouse] populations purified on the fluorescence-activated cell sorter. Gene rearrangment was assessed by measuring the loss of germ-line joining (J) segment-containing restriction fragments in B cells and 2 populations of pre-B cells. Large pre-B cells, the earliest identifiable cells in the B lineage, have rearrangements at both JH loci but do not have rearrangements at the .kappa. chain loci. H chain rearrangement occurs concurrently with, or prior to, the expression of the surface marker B220, which was used to identify and isolate pre-B cells. Small pre-B cells, which include the immediate precursors of B cells, likewise have rearrangements at both JH loci, but may also have J.kappa. rearrangements. Approximately 1/3 of the J.kappa. loci are rearranged in small pre-B cells, compared to 2/3 in .kappa. chain-expressing B cells. The small pre-B cell population is probably actively undergoing .kappa. chain gene rearrangement. The striking asynchrony in H and L chain gene rearrangement is reflected at the level of gene expression; both pre-B cell populations synthesize .mu. chains but not .kappa. L chains. H chain rearrangement is therefore a very early event in B lineage development and may begin in a cell not yet fully committed to the B lineage, whereas .kappa. rearrangement occurs just prior to the expression of surface Ig and may be a rate-limiting step in the transition from pre-B to B cells.