IGF-I resistance in virus-transformed B-lymphocytes from African Efe Pygmies

To investigate IGF-I resistance in African Efe Pygmies, we examined clonal responsiveness to IGF-I in Epstein-Barr virus-transformed B-lymphocytes from three Efe Pygmies and three American control subjects. The Efe B-lymphoblasts did not increase clonal responsiveness when incubated with IGF-I (as high as 250 micrograms/liter) in contrast to the control B-lymphoblasts which showed a bimodal dose-response with a maximal stimulation of 50% above baseline. The proliferative response of Efe B-lymphoblasts was similar to that of control B-lymphoblasts when incubated with another growth factor, phorbol 12-myristate 13-acetate, which does not activate the IGF-I receptor. These findings indicate that Efe Pygmy B-lymphoblasts are resistant to IGF-I as measured by in vitro clonal proliferation assays. Coupled with our previous report of IGF-I unresponsiveness in Efe Pygmy HTLV-II-transformed T-lymphocytes, these data suggest that IGF-I resistance is generalized and may play a central role in the etiology of short stature in this population.