RESTRICTED USE OF CATIONIC GERMLINE V-H GENE SEGMENTS IN HUMAN RH(D) RED-CELL ANTIBODIES

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.