The human red cell Rh(D) antigen elicits the production of high-affini
ty IgG antibodies, which can prevent blood transfusion and cause hemol
ytic disease of the newborn. It has been known for 20 years that Rh(D)
antibodies are among the most positively charged human serum IgGs. An
alysis by IEF of 9 human anti-Rh(D) monoclonal antibodies showed that
their isoelectric points (pi) (8.3 to 8.6) were also significantly hig
her 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 pls in IEF were corr
elated with a higher number of cationic amino acid residues in the H c
hain V regions without clustering in the complementary determining reg
ion. Computer analysis indicated that the germline V-H used in anti-Rh
(D) was selected among the most cationic segments available in the hum
an V-H repertoire or expressed in normal B cells. These results indica
te that the selection of cationic V-H segments may be an important ear
ly step in the formation of clinically relevant anti-Rh(D) and other r
ed cell antibodies, possibly to facilitate epitope binding in the nega
tively charged red cell membrane environment. (C) 1997 by The American
Society of Hematology.