AUTOANTI-RED CELL ANTIBODIES SYNTHESIZED BY PATIENTS WITH INFECTIOUS-MONONUCLEOSIS UTILIZE THE V(H)4-21 GENE SEGMENT

A significant proportion of patients with B cell tumors secrete IgM mA b that recognize a carbohydrate autoantigen (Ii) on the red cell surfa ce. The majority bear an idiotope (Id) that arises from heavy chains e ncoded by the V(H)4-21 gene segment, indicating unusual restriction of autoantibody specificity to a single V(H) gene. Polyclonal anti-Ii an tibodies are also synthesized transiently by normal B cells following certain infections, and we have analyzed the role of the V(H)4-21 gene in encoding these antibodies. Levels of Id in sera of patients follow ing infection with EBV or Mycoplasma pneumoniae were significantly rai sed (p < 0.01), and the Id-positive Ig reacted with patients' red cell s. Id-positive B cell clones were established from four EBV-infected p atients, and 6/6 of the IgM-Id agglutinated red cells. Nucleotide sequ ence analysis revealed involvement of the V(H)4-21 gene in all cases, with remarkably little change from the germ-line sequence. However, D segments were heterogeneous, and light chains differed. These results indicate that the same V(H) gene is used both by polyclonal autoantibo dies produced in response to infection, and by B cell tumors. However, the lack of mutations would not appear to give an opportunity for Ag selection to drive affinity maturation of these autoantibodies.