Differential requirement for OBF-1 during antibody-secreting cell differentiation

被引:50
作者
Corcoran, LM [1 ]
Hasbold, J
Dietrich, W
Hawkins, E
Kallies, A
Nutt, SL
Tarlinton, DM
Matthias, P
Hodgkin, PD
机构
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia
[2] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland
基金
英国医学研究理事会;
关键词
D O I
10.1084/jem.20042325
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Resting B cells can be cultured to induce antibody-secreting cell (ASC) differentiation in vitro. A quantitative analysis of cell behavior during such a culture allows the influences of different stimuli and gene products to be measured. The application of this analytical system revealed that the OBF-1 transcriptional coactivator, whose loss impairs antibody production in vivo, has two effects on ASC development. Although OBF-1 represses early T cell dependent (TD) differentiation, it is also critical for the completion of the final stages of ASC development. Under these conditions, the loss of OBF-1 blocks the genetic program of ASC differentiation so that Blimp-1/prdm1 induction fails, and bcl-6, Pax5, and AID are not repressed as in control ASC. Retroviral complementation confirmed that OBF-1 was the critical entity. Surprisingly, when cells were cultured in lipopolysaccharide to mimic T cell independent conditions, OBF-1-null B cells differentiated normally to ASC. In the OBF-1(-/-) ASC generated under either culture regimen, antibody production was normal or only modestly reduced, revealing that Ig genes are not directly dependent on OBF-1 for their expression. The differential requirement for OBF-1 in TD ASC generation was confirmed in vivo. These studies define a new regulatory role for OBF-1 in determining the cell-autonomous capacity of B cells to undergo terminal differentiation in response to different immunological signals.
引用
收藏
页码:1385 / 1396
页数:12
相关论文
共 52 条
[1]   CENTRIFUGAL ENHANCEMENT OF RETROVIRAL-MEDIATED GENE-TRANSFER [J].
BAHNSON, AB ;
DUNIGAN, JT ;
BAYSAL, BE ;
MOHNEY, T ;
ATCHISON, RW ;
NIMGAONKAR, MT ;
BALL, ED ;
BARRANGER, JA .
JOURNAL OF VIROLOGICAL METHODS, 1995, 54 (2-3) :131-143
[2]   Regulatory mechanisms that determine the development and function of plasma cells [J].
Calame, KL ;
Lin, KI ;
Tunyaplin, C .
ANNUAL REVIEW OF IMMUNOLOGY, 2003, 21 :205-230
[3]   OcaB is required for normal transcription and V(D)J recombination of a subset of immunoglobulin κ genes [J].
Casellas, R ;
Jankovic, M ;
Meyer, G ;
Gazumyan, A ;
Luo, Y ;
Roeder, RG ;
Nussenzweig, MC .
CELL, 2002, 110 (05) :575-585
[4]   OCT-2 IS REQUIRED EARLY IN T-CELL-INDEPENDENT B-CELL ACTIVATION FOR G1 PROGRESSION AND FOR PROLIFERATION [J].
CORCORAN, LM ;
KARVELAS, M .
IMMUNITY, 1994, 1 (08) :635-645
[5]  
Corcoran LM, 1999, J IMMUNOL, V163, P5836
[6]   Control of inflammation, cytokine expression, and germinal center formation by BCL-6 [J].
Dent, AL ;
Shaffer, AL ;
Yu, X ;
Allman, D ;
Staudt, LM .
SCIENCE, 1997, 276 (5312) :589-592
[7]   Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules [J].
Fehr, T ;
López-Macías, C ;
Odermatt, B ;
Torres, RM ;
Schubart, DB ;
O'Keefe, TL ;
Matthias, P ;
Hengartner, H ;
Zinkernagel, RM .
INTERNATIONAL IMMUNOLOGY, 2000, 12 (09) :1275-1284
[8]   The balance between Pax5 and Id2 activities is the key to AID gene expression [J].
Gonda, H ;
Sugai, M ;
Nambu, Y ;
Katakai, T ;
Agata, Y ;
Mori, KJ ;
Yokota, Y ;
Shimizu, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (09) :1427-1437
[9]  
Grignani F, 1998, CANCER RES, V58, P14
[10]   A B-CELL COACTIVATOR OF OCTAMER-BINDING TRANSCRIPTION FACTORS [J].
GSTAIGER, M ;
KNOEPFEL, L ;
GEORGIEV, O ;
SCHAFFNER, W ;
HOVENS, CM .
NATURE, 1995, 373 (6512) :360-362