RESTRICTED V(H) GENE USAGE BY MURINE HYBRIDOMAS DIRECTED AGAINST THE HUMAN N, BUT NOT M, BLOOD-GROUP ANTIGEN

The M and N human blood group antigens are complex glycopeptide determinants at the amino terminus of the red blood cell membrane glycoprotein, glycophorin A. The heavy and light chain variable region cDNA sequences were determined for seven murine monoclonal antibodies recognizing glycophorin A. Three of the antibodies were anti-M and four were anti-N. Each of the anti-M antibodies was composed of V(H) and V(L) regions derived from distinct germline gene families (V(H)1 (J558), V(H)4 (X24), V(H)5 (7183), V(K)5, V(K)8, and V(K)19). In contrast, all four anti-N heavy chains were composed of VH regions derived from the V(H)2 (Q52) germline gene family and all used the same J4 gene segment. In addition, two of the anti-N light chains were composed of V(K) regions from the V(K)8 germline gene family and used the J1 gene segment. Since each anti-N hybridoma was derived from different mice immunized by different protocols, these results suggest that the murine immune response to the N, but not the M, human blood group antigen is restricted.