FOLLICULAR DENDRITIC CELLS HELP RESTING B-CELLS TO BECOME EFFECTIVE ANTIGEN-PRESENTING CELLS - INDUCTION OF B7/BB1 AND UP-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES

被引:75
作者
KOSCOVILBOIS, MH
GRAY, D
SCHEIDEGGER, D
JULIUS, M
机构
[1] HAMMERSMITH HOSP, ROYAL POSTGRAD MED SCH, DEPT IMMUNOL, LONDON WI2 0NN, ENGLAND
[2] UNIV TORONTO, DEPT IMMUNOL, TORONTO M5F 1A8, ON, CANADA
关键词
D O I
10.1084/jem.178.6.2055
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.
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页码:2055 / 2066
页数:12
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