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1996-02-26
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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).