IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia

Intravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigat e this, we cloned previously a large number of phage displayed IgG Fab frag ments derived from three patients with autoimmune thrombocytopenia (AITP) t hat were specifically bound by IVIG molecules. Many of these Fabs reacted w ith platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for m any other autoantibodies. Particularly, the loci 3-30 or 3-30/3-30.5, 3-23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (V-H) and light chain V region (V-L), respectively. This suggested a specif ic interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3-30 and 3-23 are the most frequently rear ranged V-H germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role f or the development and control of the normal B cell repertoire.