The Antibody Repertoire of Early Human B Cells

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Abstract
Our previous studies have shown that a high frequency of Epstein‐Barr virus (EBV)‐immortalized cord blood (CB) and fetal liver (FL) clones produce IgM antibodies which display extensive autoreactivity for IgG Fc (rheumatoid factor, RF). To investigate further the repertoire of these early B B cells we have examined the expression of CRI associated with RF paraproteins in relation to antibody specificity and polyreactivity. CRI were detected by ELISA and/or flow cytometry using a panel of well‐characterized monoclonal antibodies defining idiotopes associated with particular VKand VH gene family products and raised against Fc‐specific paraproteins. Many of the CRI were expressed by these clones, suggesting that they may be markers of early B cells. The presence of the CRI was not always associated with Fc specificity. Three of eight CB/FL clones expressed the VKII subgroup of light chains, and two of these expressed the VK sub‐subgroup associated CRI, 17‐109. These two clones reacted with IgG Fc, and one also bound to single‐stranded DNA. The VHIII‐associated idiotope D12 was expressed on IgM from 4 out of 9 FL and 5 out of 12 CB clones. D12 and B6(also a VH‐III‐associated CRI) were coexpressed in 4 out of 5 CB clones but not in the four FL clones. Seven out of nine clones expressing these idiotopes were polyreactive. and five had Fc‐binding activity. Three of the 12 CB clones expressed the VHI‐associated conformational idiotope G8. One of 20 CLL clones expressed both B6 and D12, and another expressed both 17‐109 and the VH‐I associated G6and G8 idiotopes. Taken together, these data provide evidence for the frequent usage, in early B cells, of VK subgroups and VH‐associated idiotopes of RF paraproteins. The expression of these CRI was not a prerequisite for binding to IgG Fc. but there was a frequent association of these idiotopes with it. Differences in expression of CRI between CLL and early B‐cell clones may suggest differences in the pattern or VH usage between these subsets of B cells.