       Document 0036
 DOCN  M9620036
 TI    Cellular origin, antigen reactivity, and VH segment structure of IgM
       mAbs from AIDS lymphomas.
 DT    9602
 AU    Riboldi P; Gaidano G; Schettino EW; Knowles DM; Dalla-Favera R; Casali
       P; Department of Pathology, New York University School of Medicine,; New
       York 10016, USA.
 SO    Ann N Y Acad Sci. 1995 Sep 29;764:509-18. Unique Identifier : AIDSLINE
       MED/96049751
 AB    In the present studies we analyzed the Ag specificity, VH gene
       structure, and cellular origin of three IgM mAb-producing cell lines
       established in vitro from bioptic specimens of three AIDS patients with
       BL. We found that (i) both HBL-2 and HBL-3 IgM mAbs were cold
       agglutinins highly specific for the i blood group determinant, a self Ag
       the expression of which is dominant in the early stages of life, and
       both mAbs used somatically point-mutated VH 4-21 segments; (ii) HBL-1
       IgM mAb, the Ag-specificity of which has not been determined, used a
       putatively mutated member of the VHIII family; and (iii) both HBL-1 and
       HBL-2, but not HBL-3, cells expressed CD5 mRNA, suggesting a B-1 cell
       origin. The utilization of VH4-21 by the HBL-2 and HBL-3 cold
       agglutinins is consistent with the usage of this gene segment by all the
       reported pathogenic except the naturally occurring cold agglutinins.
       This restricted VH gene usage may reflect an inherent affinity of the
       germline VH4-21 gene product for the i/I carbohydrate structure, and,
       perhaps, an overrepresentation of VH4-21 in the human early and late
       B-cell repertoire. Consistent with both an early and late developmental
       expression of the VH4-21 gene is the B-1 and B-2 cellular origin of the
       two VH4-21+ cold agglutinins reported here. Thus, the two cold
       agglutinin autoantibodies possibly emerged at different stages of the
       natural history of the B-cell repertoires of these patients and might
       display a different temporal relationship, as discussed below, to the
       time of emergence of the respective tumoral cells. The somatically
       mutated status of the HBL-2 and HBL-3 mAb VH segments was suggested by
       the monomorphism of the human VH4-21 gene, the extension of the
       nucleotide differences to the, in general, highly conserved JH segment;
       and it was formally proved in HBL-3 mAb. Positive selection by Ag of the
       R mutations in the HBL-2 and HBL-3 mAb VH segments was suggested by the
       differential R:S mutation ratios in the CDRs and FRs (HBL-2 mAb, 5.0 and
       1.1, respectively; HBL-3 mAb, 2.2 and 0.3, respectively) but not
       substantiated by appropriate statistical analysis according to the
       binomial distribution model.(ABSTRACT TRUNCATED AT 400 WORDS)
 DE    Amino Acid Sequence  Antibodies, Monoclonal/*GENETICS  Antibodies,
       Neoplasm/*GENETICS  Antibody Specificity  Base Sequence  Clonal Deletion
       Comparative Study  DNA Mutational Analysis  DNA, Neoplasm/GENETICS
       *Gene Expression Regulation, Neoplastic  *Genes, Immunoglobulin
       Hemagglutinins/GENETICS  Human  I Blood-Group System/IMMUNOLOGY
       IgM/*GENETICS  Immunoglobulin Variable Region/*GENETICS
       Immunoglobulins, Heavy-Chain/*GENETICS  Lymphoma,
       AIDS-Related/*GENETICS/PATHOLOGY  Lymphoma, B-Cell/*GENETICS/PATHOLOGY
       Molecular Sequence Data  Point Mutation  Receptors, Antigen,
       B-Cell/*GENETICS  Sequence Alignment  Sequence Homology  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Tumor Cells, Cultured
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

