Effect of 51p1-related gene copy number (V1-69 locus) on production of hepatitis C-associated cryoglobulins

Monoclonal IgM in type II mixed cryoglobulins (MC) preferentially use 51p1- related immunoglobulin V-H genes. In normal preimmune B lymphocytes, 51p1-r elated gene expression is proportional to the germ-line gene dosage, which can be 0-4. To determine whether 51p1-related gene dosage influences the oc currence of type II MC or the V-H gene bias in cryoglobulin IgM, we studied 47 patients chronically infected with hepatitis C virus (HCV), 24 MC+, 23 MC-. By Western analysis, 11 cryoprecipitate IgM (46%) were detected by G6 (a marker for 51p1-related gene products), eight (33%) by Staphylococcal Pr otein A (a V(H)3 family marker), and five (21%) by neither, indicating a 23 -fold bias favouring 51p1-related genes. All 11 MC+, G6(+) patients possess ed greater than or equal to 1 copy of a 51p1-related gene; nine of the 36 o thers had none. The mean copy number of 51p1-related genes was greater in M C+ than MC- patients, and in MC+, G6(+) patients versus the 36 others (P < 0.04), but significant differences were not seen in analyses restricted to patients with greater than or equal to 1 copy of a 51p1-related gene. We co nclude that when a 51p1-related gene is present, a strong bias favours G6() IgM in HCV-associated type II MC, but this bias is not greatly increased by a high dosage of 51p1-related genes. Furthermore, patients lacking 51p1- related genes also produce MC, but with G6(-) IgM.