Abstract
V(D)J recombination occurs during the antigen-independent early steps of B-cell ontogeny. Multiple IgH cis-regulatory elements control B-cell ontogeny. IGCR1 (intergenic control region 1), the DQ52 promoter/enhancer, and the intronic Emu enhancer, all three located upstream of Cmu, have important roles during V(D)J recombination, whereas there is no clue about a role of the IgH regulatory region (RR) encompassing the four transcriptional enhancers hs3a, hs1,2, hs3b, and hs4 during these early stages. To clarify the role of the RR in V(D)J recombination, we totally deleted it in the mouse genome. Here, we show that V(D)J recombination is unaffected by the complete absence of the IgH RR, highlighting that this region only orchestrates IgH locus activity during the late stages of B-cell differentiation. In contrast, the earliest antigen-independent steps of B-cell ontogeny would be under the control of only the upstream Cmu elements of the locus.
Highlights
We examined the effect of deletion of the heavy chain regulatory region (RR) on VDJ recombination in B-cells
V(D)J Usage Is Not Affected in 3Ј regulatory region (3ЈRR)-deficient Mouse Pre-B-cells—We investigated V(D)J usage in 3ЈRR-deficient mice compared with 129 WT mice
These results suggest that V(D)J rearrangements normally occurred in bone marrow CD25ϩ B-cells of 3ЈRR-deficient mice, and there was no indication of any gross alteration in the V(D)J recombination process
Summary
We examined the effect of deletion of the heavy chain regulatory region (RR) on VDJ recombination in B-cells. During the antigenindependent step of B-cell ontogeny, the V(D)J recombination process within the IgH locus allows the assembly and expression of the functional heavy chain gene [3].
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