The Antibody Repertoire of Early Human B Cells.

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 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 V_k and V_H 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 V_kIII subgroup of light chains, and two of these expressed the V_kIII sub-subgroup associated CRL 17-109. These two clones reacted with IgG Fc, and one also hound lo single-stranded DNA. The V nil [-associated idiotope DI2 was expressed on IgM from 4 out of 9 FL and 3 out of 12 CB clones. D12 and B6 (also a V_H-III-associated CRI) were coexpressed in 4 out of 5 CB clones but not in the lour FL clones. Seven out of nine clones expressing these idiotopes were polyreactive. and five had Fc-binding activity. Three of the 12 CB clone expressed the V_HI-associated conformational idiotope G8. One of 20 CLL clones expressed both B6 and D12, and another expressed both 17-109 and the Vulassociated G6 and G8 idiotopes. Taken together, these data provide evidence for the frequent usage, in early B cells, of V_k subgroups and V_H-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 of Vu usage between these subsets of B cells. [ABSTRACT FROM AUTHOR]