Antibodies against different chronic viruses, including hepatitis C virus (HCV), express a public cross-reactive idiotype (Id) designated as 1F7. The prominence of this Id may reflect selective engagement of B1 B cells by chronic pathogens. We investigated this by comparing 1F7 Id expression on CD5 + and CD5 À B cells, total IgG, total IgM and anti-HCV core antibodies in different HCV exposure settings. By flow cytometry, we observed a selective increase in 1F7 Id + CD5 + B cells in chronic HCV infection. 1F7 Id levels in different immunoglobulin compartments were measured by enzyme-linked immunosorbent assay. 1F7 Id expression was prominent in anti-HCV core antibodies of B90% of 141 HCV-exposed individuals tested. In the Canadian and Armenian study groups, participants who spontaneously cleared HCV infection had lower median 1F7 Id levels on total plasma IgG and anti-HCV core antibodies. Armenian spontaneous clearers, who were younger and more recently infected than their Canadian counterparts, also had had lower median 1F7 Id levels on total plasma IgM. Engagement by HCV of B-cell receptors within, or overlapping with the CD5 + B1 B-cell repertoire is reflected in the production of 1F7 Id + anti-HCV antibodies and expansion of 1F7 Id + CD5 + B cells. Higher 1F7 Id expression levels are associated with chronic infection. Idiotopes are antigenic determinants within immunoglobulin (Ig) or T-cell receptor variable (V) regions. Although the idiotype (Id) of an Ig or T-cell receptor represents the aggregate of idiotopes within its V region, antibodies (Ab) against individual idiotopes are termed anti-idiotypic. Therefore, V region reactivity of Ig preparations with a monoclonal Ab (mAb) denotes the expression of an Id that is named in reference to the mAb, by convention. The significance of Id distribution within individual antibody repertoires and throughout populations has been extensively studied in relation to immune regulation, autoimmunity and infection. 1 During B-cell ontogeny, idiotypes defined by mAb assume a level of prominence reflecting their frequency of generation through the largely random processes of V gene rearrangement, junctional modification and combinatorial pairing that underly B-cell receptor assembly. If the relevant idiotope maps within germ-lineencoded V, diversity (D) or joining (J) gene sequences, the Id will be public (often present at meaningful levels in the population) and crossreactive (on antibodies of different specificity). In contrast, if the idiotope reflects a particular V heavy (H) chain/V light (L) chain combination incorporating idiosyncratic VD, VJ, or DJ junctions, the corresponding Id will reach meaningful levels only after antigenic selection or cellular transformation. As this type of Id is more often private (uncommon in the population) and restricted to antibodies of like specificity, its emergence as a public Id in certain situations may show common structural aspects of immunoglobulin networks.Biased Ig V gene segment usage, antigenic selection and possibly, the v...