Altered VH6-D-JH repertoire in human insulin-dependent diabetes mellitus and autoimmune idiopathic thrombocytopenic purpura

We have characterized the peripheral B cell repertoire in T cell-mediated i nsulin-dependent diabetes mellitus (IDMM) and in B cell-mediated autoimmune idiopathic thrombocytopenic purpura (AITP). The VH6-containing repertoire in adult patients with IDDM or AITP and healthy control subjects was invest igated by PCR amplification using VH6- and JH-specific primers. Nucleotide sequence analysis of VH6-D-JH rearrangements showed an abnormally high freq uency of somatic mutations in non-functional rearrangements from diabetic ( 3.58 %) as well as AITP patients (3.18 %), compared to controls (0.4 % and 1.43 %, respectively; p < 0.05). In contrast, the mutation frequency among functional rearrangements was 2.4-3 times lower in patients compared to con trols (p < 0.05). Detailed analysis of the VH6 genes carrying mutations sho wed that the underlying mechanism for this observation is probably differen t for the two diseases. Analysis of D- and JH gene usage revealed additiona l deviations from the normal pattern. Taken together, these results suggest defects in the mechanisms controlling selection of the B cell repertoire i n patients with IDDM or AITP.