Lymph node germinal centers form in the absence of follicular dendritic cell networks

被引:51
作者
Koni, PA
Flavell, RA
机构
[1] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA
关键词
lymphotoxin beta; knockout mice; follicular dendritic cells; germinal centers; B cell memory;
D O I
10.1084/jem.189.5.855
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin beta-deficient mice form GC cell dusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin beta-deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response war of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later.
引用
收藏
页码:855 / 864
页数:10
相关论文
共 66 条
[1]   Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen [J].
Ahearn, JM ;
Fischer, MB ;
Croix, D ;
Goerg, S ;
Ma, MH ;
Xia, JR ;
Zhou, XN ;
Howard, RG ;
Rothstein, TL ;
Carroll, MC .
IMMUNITY, 1996, 4 (03) :251-262
[2]   Complementation of lymphotoxin α knockout mice with tumor necrosis factor-expressing transgenes rectifies defective splenic structure and function [J].
Alexopoulou, L ;
Pasparakis, M ;
Kollias, G .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (04) :745-754
[3]   Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice [J].
Alimzhanov, MB ;
Kuprash, DV ;
KoscoVilbois, MH ;
Luz, A ;
Turetskaya, RL ;
Tarakhovsky, A ;
Rajewsky, K ;
Nedospasov, SA ;
Pfeffer, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (17) :9302-9307
[4]   ANTIBODY ENGINEERING FOR THE ANALYSIS OF AFFINITY MATURATION OF AN ANTI-HAPTEN RESPONSE [J].
ALLEN, D ;
SIMON, T ;
SABLITZKY, F ;
RAJEWSKY, K ;
CUMANO, A .
EMBO JOURNAL, 1988, 7 (07) :1995-2001
[5]  
ANDROLEWICZ MJ, 1992, J BIOL CHEM, V267, P2542
[6]  
BANKS TA, 1995, J IMMUNOL, V155, P1685
[7]   HEAVY-CHAIN VARIABLE REGION CONTRIBUTION TO THE NPB FAMILY OF ANTIBODIES - SOMATIC MUTATION EVIDENT IN A GAMMA-2A VARIABLE REGION [J].
BOTHWELL, ALM ;
PASKIND, M ;
RETH, M ;
IMANISHIKARI, T ;
RAJEWSKY, K ;
BALTIMORE, D .
CELL, 1981, 24 (03) :625-637
[8]   LYMPHOTOXIN-BETA, A NOVEL MEMBER OF THE TNF FAMILY THAT FORMS A HETEROMERIC COMPLEX WITH LYMPHOTOXIN ON THE CELL-SURFACE [J].
BROWNING, JL ;
NGAMEK, A ;
LAWTON, P ;
DEMARINIS, J ;
TIZARD, R ;
CHOW, EPC ;
HESSION, C ;
OBRINEGRECO, B ;
FOLEY, SF ;
WARE, CF .
CELL, 1993, 72 (06) :847-856
[9]   Signaling through the lymphotoxin beta receptor induces the death of some adenocarcinoma tumor lines [J].
Browning, JL ;
Miatkowski, K ;
Sizing, I ;
Griffiths, D ;
Zafari, M ;
Benjamin, CD ;
Meier, W ;
Mackay, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (03) :867-878
[10]   Follicular dendritic cells (FDC) in retroviral infection: Host/pathogen perspectives [J].
Burton, GF ;
Masuda, A ;
Heath, SL ;
Smith, BA ;
Tew, JG ;
Szakal, AK .
IMMUNOLOGICAL REVIEWS, 1997, 156 :185-197