Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation
CE Teh, K Horikawa, CN Arnold, B Beutler, EM Kucharska, CG Vinuesa, EM Bertram, CC Goodnow, A Enders
GENES AND IMMUNITY | NATURE PUBLISHING GROUP | Published : 2013
To identify rate-limiting steps in T cell-independent type 2 antibody production against polysaccharide antigens, we performed a genome-wide screen by immunizing several hundred pedigrees of C57BL/6 mice segregating N-ethyl-N-nitrosurea-induced mis-sense mutations. Two independent mutations, Tilcara and Untied, were isolated that semi-dominantly diminished antibody against polysaccharide but not protein antigens. Both mutations resulted from single-amino-acid substitutions within the kinase domain of protein kinase C-β (PKCβ). In Tilcara, a Ser552>Pro mutation occurred in helix G, in close proximity to a docking site for the inhibitory N-terminal pseudosubstrate domain of the enzyme, resulti..View full abstract
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
We thank the staff of the ANU Bioscience Services, the Scripps Research Institute vivarium, the Australian Phenomics Facility, and the JCSMR Flow Cytometry Facility for expert technical services. This work was supported by grants from the Clive and Vera Ramaciotti Foundation, NIH, Wellcome Trust and the NHMRC.