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.
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.
Lydyard
P M
PM
Departments of Immunology, University College, London, UK.
Quartey-Papafio
R P
RP
Bröker
B M
BM
MacKenzie
L
L
Hay
F C
FC
Youinou
P Y
PY
Jefferis
R
R
Mageed
R A
RA
D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D005312:Fetal Blood / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000032:analysis; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007135:Immunoglobulin Variable Region / Q000032:analysis*; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000196:embryology*; D005810:Multigene Family; D012217:Rheumatoid Factor / Q000032:analysis*
D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor