Restricted use of cationic germline V(H) gene segments in human Rh(D) red
cell antibodies
G Boucher, H Broly and R Lemieux
The Canadian Red Cross Society, Blood Services, Ste-Foy, Quebec, Canada.
The human red cell Rh(D) antigen elicits the production of high- affinity
IgG antibodies, which can prevent blood transfusion and cause hemolytic
disease of the newborn. It has been known for 20 years that Rh(D)
antibodies are among the most positively charged human serum IgGs. Analysis
by IEF of 9 human anti-Rh(D) monoclonal antibodies showed that their
isoelectric points (pI) (8.3 to 8.6) were also significantly higher than
the average pI of serum IgGs (7.0 to 8.5). Sequencing of the anti-Rh(D) H
and L chains cDNAs showed a preferential use of V(H)1, V(H)3, J(H)6, and
V(kappa)1 gene segments. The high pIs in IEF were correlated with a higher
number of cationic amino acid residues in the H chain V regions without
clustering in the complementary determining region. Computer analysis
indicated that the germline V(H) used in anti-Rh(D) was selected among the
most cationic segments available in the human V(H) repertoire or expressed
in normal B cells. These results indicate that the selection of cationic
V(H) segments may be an important early step in the formation of clinically
relevant anti-Rh(D) and other red cell antibodies, possibly to facilitate
epitope binding in the negatively charged red cell membrane environment.
Volume 89,
Issue 9,
pp. 3277-3286,
05/01/1997
Copyright © 1997 by The American Society of Hematology
