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Titolo:
OVEREXPRESSION OF BCL-2 ALTERS USAGE OF MUTATIONAL HOT-SPOTS IN GERMINAL CENTER B-CELLS
Autore:
KUO P; ALBAN A; GEBHARD D; DIAMOND B;
Indirizzi:
ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,MORRIS PK AVE,ROOM 405 FORSCHHEIMER BRONX NY 10461 ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL BRONX NY 10461
Titolo Testata:
Molecular immunology
fascicolo: 14, volume: 34, anno: 1997,
pagine: 1011 - 1018
SICI:
0161-5890(1997)34:14<1011:OOBAUO>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRIMARY IMMUNE-RESPONSE; SOMATIC MUTATION; ANTIGEN; EXPRESSION; APOPTOSIS; ANTIBODY; GENES; DEATH; MICE; MECHANISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
P. Kuo et al., "OVEREXPRESSION OF BCL-2 ALTERS USAGE OF MUTATIONAL HOT-SPOTS IN GERMINAL CENTER B-CELLS", Molecular immunology, 34(14), 1997, pp. 1011-1018

Abstract

Bcl-2 is an anti-apoptotic gene important in B cell development. In order to study how apoptosis regulates somatic hypermutation and selection of B cell clones in the germinal center, we examined the antibody response to phosphorylcholine (PC) in transgenic mice overexpressing bcl-2 in the B cell compartment. The anti-PC antibody response is dominated by the S107V1 variable region heavy chain gene. We, therefore, analyzed S107V1-encoded heavy chains from germinal center cells. The proportion of germinal center sequences that were mutated, and the frequency of mutations did not differ significantly between the two groups of mice. No significant differences were found in the clustering of replacement mutations in the complementarity determining regions (CDRs) and in replacement to silent (R:S) mutation ratios. A significant difference between bcl-2 transgenic mice and controls, however, was found in the targeting of mutations to oligonucleotide motifs presumed to be mutational ''hot spots. '' While non-transgenic mice displayed the expected clustering of mutations in hot spots, mutations from bcl-2 transgenic mice lacked this pattern. This observation suggests that the mechanism for somatic hypermutation includes two distinct functions, a nonspecific mutational apparatus and a mechanism to target mutation to hot spots, and that in certain circumstances these functions may be uncoupled. (C) 1997 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 04:04:05