Autosomal primary immunodeficiencies affecting human bone marrow B-cell differentiation

Since the initial report of X-linked agammaglobulinemia by Bruton, numerous autosomal primary immune deficiencies affecting early B-cell differentiati on have been described in humans. The identification of these autosomal mut ations has been facilitated by phenotype comparison with knockout mice. In mice, defects in B-cell development have been observed after disruption of genes encoding transcription factors, the interleukin-7 pathways as well as structural or signaling components of the pre-B-cell receptor. In general, the phenotypes of primary immune deficiencies in humans correlate with tho se observed in mutant mice, validating the use of the mouse model approach. In addition, we report a follow-up analysis of an autosomal primary defici ency in a young female patient born from consanguinous parents and characte rized by the absence of pre-B and B-cell compartments. The patient's gene d efect was identified as a cytosine insertion at the beginning of the CHI ex on of the Ig mu gene. resulting in a stop codon at position 48 and the abse nce of Ig mu chain expression. The precise phenotype of this patient is com pared to other autosomal primary immunodeficiencies affecting humans and mi ce.