Ddx3x regulates B-cell development and light chain recombination in mice

BioRxiv : the Preprint Server for Biology
Ke LiuStephen Waggoner

Abstract

Ddx3x encodes a DEAD box RNA helicase implicated in antiviral immunity and tumorigenesis. We find that hematopoietic Ddx3x deficiency in Vav1-Cre mice (ΔDdx3x) results in altered leukocyte composition of secondary lymphoid tissues, including a marked reduction in mature B cells. This paucity of peripheral B cells is associated with deficits in B-cell development in the bone marrow, including reduced frequencies of small pre-B cells. Bone marrow chimera experiments reveal a B-cell intrinsic effect of Ddx3x deletion. Mechanistically, ΔDdx3x small pre-B cells exhibit lower expression of Brwd1, a histone reader that restricts recombination at the immunoglobulin kappa (Igκ) locus. In fact, the B-cell deficits in ΔDdx3x mice resemble those of Brwd1 mutant mice, and both strains of mice exhibit defective Igκ rearrangement in small pre-B cells. The contribution of Ddx3x to Brwd1 expression and light chain rearrangement constitutes the first evidence of a role for an RNA helicase in promoting B-cell development.

Related Concepts

B-Lymphocytes
Bone Marrow
Gene Deletion
Gene Rearrangement
Histones
Immunoglobulin G
Leukocytes
Lymphoid Tissue
Laboratory mice
Recombination, Genetic

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