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Titolo:
INTERLEUKIN-6 INFLUENCES GERMINAL CENTER DEVELOPMENT AND ANTIBODY-PRODUCTION VIA A CONTRIBUTION OF C3 COMPLEMENT COMPONENT
Autore:
KOPF M; HERREN S; WILES MV; PEPYS MB; KOSCOVILBOIS MH;
Indirizzi:
SERONO PHARMACEUT RES INST,14 CHEMIN AULX CH-1228 GENEVA SWITZERLAND BASEL INST IMMUNOL CH-4005 BASEL SWITZERLAND GLAXO WELLCOME RES & DEV LTD,GENEVA BIOMED RES INST CH-1228 GENEVA SWITZERLAND MAX PLANCK INST MOL GENET D-14195 BERLIN GERMANY HAMMERSMITH HOSP,IMMUNOL MED UNIT LONDON W12 0NN ENGLAND
Titolo Testata:
The Journal of experimental medicine
fascicolo: 10, volume: 188, anno: 1998,
pagine: 1895 - 1906
SICI:
0022-1007(1998)188:10<1895:IIGCDA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOLLICULAR DENDRITIC CELLS; PRIMARY IMMUNE-RESPONSE; GROWTH-FACTOR ACTIVITY; TUMOR-NECROSIS-FACTOR; T-DEPENDENT ANTIGEN; B-CELL; TRANSGENIC MICE; INTERLEUKIN-6-DEFICIENT MICE; HUMORAL IMMUNITY; ACCESSORY CELLS;
Keywords:
GERMINAL CENTER; INTERLEUKIN 6; COMPLEMENT; ANTIBODY; FOLLICULAR DENDRITIC CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
91
Recensione:
Indirizzi per estratti:
Citazione:
M. Kopf et al., "INTERLEUKIN-6 INFLUENCES GERMINAL CENTER DEVELOPMENT AND ANTIBODY-PRODUCTION VIA A CONTRIBUTION OF C3 COMPLEMENT COMPONENT", The Journal of experimental medicine, 188(10), 1998, pp. 1895-1906

Abstract

Mice rendered deficient for interleukin (IL) 6 by gene targeting wereevaluated for their response to T cell-dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in thewild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). Tcell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6-deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti-mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3-deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6-deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 00:37:09