- Paper Report
- Open Access
Molecular nature of hyper-IgM syndrome type 2
- Thomas Dorner1
© Current Science Ltd 2000
- Published: 1 November 2000
- B cells
- class switching
- somatic hypermutation
- V genes
A rare human immunodeficiency disease, the hyper-IgM syndrome (HIGM), is characterized by normal or elevated serum IgM levels, a lack of detectable IgG, IgA, and IgE and a high susceptibility to bacterial infections. Whereas the molecular basis of the X-linked form (HIGM1) is mutations in the gene coding for CD40L, another HIGM syndrome (HIGM2) has been described with autosomal recessive inheritance, normal CD40L sequences and CD40L/CD40 membrane expression. The molecular nature of the intrinsic defect apparently originating in B cells in HIGM2 patients has not been identified previously.
This study identified 10 independent mutations in the human activation-induced cytidine deaminase (AID) gene in 18 patients with HIGM2 from 12 unrelated families. Almost all of these patients had high levels of IgM and very low IgG and IgA levels. Through sequencing of transcripts using V3-23 gene rearrangements, the authors found a mutational frequency of 0-0.4% in CD19+ B cells and 0-0.9% in CD27+/CD19+B cells as compared to 2.6-6.3% in normal.
Strikingly, a marked follicular hyperplasia of germinal centres (GCs) was identified in these patients who typically exhibit lymphadenopathy. These GCs were about 5 to 10 times larger than GCs from controls.
AID sequencing, RT-PCR, northern blot, immunohistochemical analysis of tonsil sections
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