Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination.
Proc Natl Acad Sci U S A
; 110(39): 15770-5, 2013 Sep 24.
Article
in En
| MEDLINE
| ID: mdl-24019479
ABSTRACT
Preceding antibody constant regions are switch (S) regions varying in length and repeat density that are targets of activation-induced cytidine deaminase. We asked how participating S regions influence each other to orchestrate rearrangements at the IgH locus by engineering mice in which the weakest S region, Sε, is replaced with prominent recombination hotspot Sµ. These mice produce copious polyclonal IgE upon challenge, providing a platform to study IgE biology and therapeutic interventions. The insertion enhances ε germ-line transcript levels, shows a preference for direct vs. sequential switching, and reduces intraswitch recombination events at native Sµ. These results suggest that the sufficiency of Sµ to mediate IgH rearrangements may be influenced by context-dependent cues.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombination, Genetic
/
Immunoglobulin E
/
Immunoglobulin Class Switching
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2013
Document type:
Article