NATURALLY-OCCURRING ANTI-I/1 COLD AGGLUTININS MAY BE ENCODED BY DIFFERENT V(H)3 GENES AS WELL AS THE V(H)4.21 GENE SEGMENT

作者：JEFFERIES LC^*; CARCHIDI CM; SILBERSTEIN LE

来源：Journal of Clinical Investigation, 1993, 92(6): 2821-2833.

DOI：10.1172/JCI116902

• IMMUNOGLOBULIN
• AUTOANTIBODY
• RED BLOOD CELL
• COLD AGGLUTININ
• AUTOIMMUNITY

In the current study, we wished to determine if the V regions encoding the naturally occurring anti-i/I ('old Agglutinins (anti-i/I CA) differ from pathogenic anti-i/I CA that are exclusively encoded by the V(H)4.21 gene. After EBV transformation of B lymphocytes, we generated one anti-I secreting clone from each of two individuals; clone 4G ( individual CM, PBL) and clone Spl (individual SC, spleen). Clone 4C expresses a V(H)3 gene sequence that is 92% homologous to the germline gene WHG26. Clone Sp1 also expresses a V(H)3 gene that is 98% homologous to the fetally rearranged M85/20P1 gene. Another clone, Sp2 (anti-i specificity), from individual SC is 98% homologous to the germline gene V(H)4.21. For correlation, we studied anti-i/I CA fractions purified from 15 normal sera and found no or relatively small amounts of 9G4 (V(H)4.21 related idiotype) reactive IgM. Five cold agglutinin fractions contained large amounts of V(H)3-encoded IgM (compared to pooled normal IgM) by virtue of their binding to modified protein Staph A (SPA), and absorption of three CA fractions with modified SPA specifically removed anti-i/I binding specificity entirely. Collectively, the data indicate that naturally occurring anti-i/I CA may be encoded to a large extent by non-V(H)4.21-related genes, and that the V(H)4.21 gene is not uniquely required for anti-i / I specificity.

• 出版日期1993-12