scholarly journals Immunoglobulin class switch recombination: study through human natural mutants

2008 ◽  
Vol 364 (1517) ◽  
pp. 577-582 ◽  
Author(s):  
Anne Durandy

Immunoglobulin class switch recombination deficiencies in humans are exquisite models to analyse the mechanisms of class switch recombination (CSR). Besides defects in CD40L/CD40 interaction, others result from an intrinsic B-cell deficiency. The recent elucidation of the molecular basis of some of them has made it possible to delineate the molecular events involved in antibody maturation. Activation-induced (cytidine) deaminase (AID) and uracil-N-glycosylase deficiencies have demonstrated the role of AID as the inducer of DNA lesions in switch and variable regions. However, most of these CSR deficiencies remain molecularly undefined. Their characterization would lead to a better understanding of the complex machinery involved in CSR.

2002 ◽  
Vol 195 (9) ◽  
pp. 1193-1198 ◽  
Author(s):  
F. Nina Papavasiliou ◽  
David G. Schatz

Activation of B cells by antigen fuels two distinct molecular modifications of immunoglobulin (Ig) genes. Class-switch recombination (CSR) replaces the Igμ heavy chain constant region with a downstream constant region gene, thereby altering the effector function of the resulting antibodies. Somatic hypermutation (SHM) introduces point mutations into the variable regions of Ig genes, thereby changing the affinity of antibody for antigen. Mechanistic overlap between the two reactions has been suggested by the finding that both require the activation-induced cytidine deaminase (AID). It has been proposed that AID initiates both CSR and SHM by activating a common nuclease. Here we provide evidence that cells lacking AID, or expressing a dominant negative form of the protein, are still able to incur DNA lesions in SHM target sequences. The results indicate that an intact cytidine deaminase motif is required for AID function, and that AID acts downstream of the initial DNA lesions in SHM.


2003 ◽  
Vol 987 (1) ◽  
pp. 1-8 ◽  
Author(s):  
ILMI OKAZAKI ◽  
KIYOTSUGU YOSHIKAWA ◽  
KAZUO KINOSHITA ◽  
MASAMICHI MURAMATSU ◽  
HITOSHI NAGAOKA ◽  
...  

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