Novel antibody switching defects in human patients
John P. Manis, Frederick W. Alt
John P. Manis, Frederick W. Alt
Published July 1, 2003
Citation Information: J Clin Invest. 2003;112(1):19-22. https://doi.org/10.1172/JCI19091.
View: Text | PDF
Commentary

Novel antibody switching defects in human patients

Abstract

Hyper-IgM syndrome (HIGM) is a primary immunodeficiency characterized by normal to elevated serum levels of IgM and low levels or the absence of IgG, IgA, and IgE. A new study AID expression in nonlymphoid cells (see related article on pages 136–142) characterizes HIGM type 4, a previously undocumented defect in antibody gene diversification caused by a selective block in class-switch recombination, providing significant insight towards understanding HIGM immunodeficiencies.

Authors

John P. Manis, Frederick W. Alt

×

Figure 1

Options: View larger image (or click on image) Download as PowerPoint
(a) The rearranged V(D)J exon is located immediately upstream of the μ c...
(a) The rearranged V(D)J exon is located immediately upstream of the μ constant region with all other classes of murine constant region genes lying downstream, with each (except Cδ) preceded by repetitive DNA sequences (termed switch (S) regions) that are between 1-12 kb in length. (b) The variable region exon or S regions targeted for modification are rendered accessible by transcription. Secondary structures, shown here for S regions, are formed and allow for direct SS DNA modification by AID, resulting in dU/dG mismatches. Differential sensing, processing, and resolution of these mismatches results in distinct outcomes for CSR or SHM.