The antibody repertoire of early human B cells. III. Expression of cross-reactive idiotopes characteristic of certain rheumatoid factors and identifying V kappa III, VHI, and VHIII gene family products

Scand J Immunol. 1990 Dec;32(6):709-16. doi: 10.1111/j.1365-3083.1990.tb03214.x.

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 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 kappa and 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 V kappa III subgroup of light chains, and two of these expressed the V kappa III 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 VHIII-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 VHI-associated G6 and G8 idiotopes. Taken together, these data provide evidence for the frequent usage, in early B cells, of V kappa 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 of VH usage between these subsets of B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • Cross Reactions
  • Fetal Blood / immunology*
  • Gene Expression
  • Humans
  • Immunoglobulin Heavy Chains / analysis
  • Immunoglobulin Idiotypes / analysis
  • Immunoglobulin M / analysis
  • Immunoglobulin Variable Region / analysis*
  • Immunoglobulin kappa-Chains / analysis
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Liver / cytology
  • Liver / embryology*
  • Multigene Family
  • Rheumatoid Factor / analysis*

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Idiotypes
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Rheumatoid Factor