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V gene usage by seven hybrids derived from CD5+ B-cell chronic lymphocytic
leukemia and displaying autoantibody activity
O Pritsch, C Magnac, G Dumas, C Egile and G Dighiero
Unite d'Immunohematologie et d'Immunopathologie, Institut Pasteur, Paris,
France.
We report here the complete heavy and light chain variable region sequences
of seven heterohybridomas derived from CD5+ chronic lymphocytic leukemia
(CLL) B lymphocytes and displaying natural autoantibody activity. The three
hybrids displaying a polyreactive pattern of binding used VH4 family
members, ie, the VH4-18 gene in germinal configuration in two cases and a
VH4 gene with 90% homology with VH4-21 for the third one. A hybrid
expressing anti-Sm activity used a VH3 family member with 95.26% homology
with the 30P1 gene. The three hybrids exclusively displaying rheumatoid
factor activity expressed VH1 family genes: 51P1 gene for two (in germinal
configuration in one, and with 93.2% homology in the other), whereas the
third one used the V1-3b gene (98.8% homology). Definitive homology with
known germline D segments was found for four of the seven hybrids (DN2 in 3
and DLR4 in 1) and JH use appeared to be random. The three hybrids
displaying polyreactive activity expressed V kappa I, V lambda III, and V
lambda II genes, all in germinal configuration. Among the three hybrids
with rheumatoid factor activity, two used the same V kappa II gene with,
respectively, 98% and 96% homology with a gene previously described; the
third used a V lambda I gene in germinal configuration. Finally, the clone
with anti-Sm activity used a V lambda III gene having 97% homology with a
germinal gene. Overall, these results attempt to establish the relationship
between frequent self- reactivity observed in CD5+ B-CLL and V gene usage.
For VH genes, they confirm overexpression of the 51P1 gene in B-CLL and
suggest nonstochastic use of two VH4 genes (4-21 and 4-18). For VL genes,
available information is too scarce to lead to firm conclusions.
Volume 82,
Issue 10,
pp. 3103-3112,
11/15/1993
Copyright © 1993 by The American Society of Hematology
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