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Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment.
Journal of Clinical Investigation 1993 December
In the current study, we wished to determine if the V regions encoding the naturally occurring anti-i/I Cold Agglutinins (anti-i/I CA) differ from pathogenic anti-i/I CA that are exclusively encoded by the VH4.21 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 Sp1 (individual SC, spleen). Clone 4G expresses a VH3 gene sequence that is 92% homologous to the germline gene WHG26. Clone Sp1 also expresses a VH3 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 VH4.21. For correlation, we studied anti-i/I CA fractions purified from 15 normal sera and found no or relatively small amounts of 9G4 (VH4.21 related idiotype) reactive IgM. Five cold agglutinin fractions contained large amounts of VH3-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-VH4.21-related genes, and that the VH4.21 gene is not uniquely required for anti-i/I specificity.
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