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Research Article Free access | 10.1172/JCI116902

Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment.

L C Jefferies, C M Carchidi, and L E Silberstein

Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia 19104.

Find articles by Jefferies, L. in: JCI | PubMed | Google Scholar

Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia 19104.

Find articles by Carchidi, C. in: JCI | PubMed | Google Scholar

Hospital of the University of Pennsylvania, Department of Pathology and Laboratory Medicine, Philadelphia 19104.

Find articles by Silberstein, L. in: JCI | PubMed | Google Scholar

Published December 1, 1993 - More info

Published in Volume 92, Issue 6 on December 1, 1993
J Clin Invest. 1993;92(6):2821–2833. https://doi.org/10.1172/JCI116902.
© 1993 The American Society for Clinical Investigation
Published December 1, 1993 - Version history
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Abstract

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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