Editing antigen presentation: Antigen transfer between human B lymphocytes and macrophages mediated by class a scavenger receptors

被引:31
作者
Harvey, Bohdan P. [1 ]
Quan, Timothy E. [1 ]
Rudenga, Benjamin J. [1 ]
Roman, Robert A. [1 ]
Craft, Joe [1 ]
Mamula, Mark J. [1 ]
机构
[1] Yale Univ, Sch Med, Dept Internal Med, Rheumatol Sect, New Haven, CT 06520 USA
基金
美国国家卫生研究院;
关键词
D O I
10.4049/jimmunol.181.6.4043
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
B lymphocytes can function independently as efficient APCs. However, our previous studies demonstrate that both dendritic cells and macrophages are necessary to propagate immune responses initiated by B cell APCs. This finding led us to identify a process in mice whereby Ag-specific B cells transfer Ag to other APCs. In this study, we report the ability and mechanism by which human B lymphocytes can transfer BCR-captured Ag to macrophages. The transfer of Ag involves direct contact between the two cells followed by the capture of B cell-derived membrane and/or intracellular components by the macrophage. These events are abrogated by blocking scavenger receptor A, a receptor involved in the exchange of membrane between APCs. Macrophages acquire greater amounts of Ag in the presence of specific B cells than in their absence. This mechanism allows B cells to amplify or edit the immune response to specific Ag by transferring BCR-captured Ag to other professional AM, thereby increasing the frequency of its presentation. Ag transfer may perpetuate chronic autoimmune responses to specific self-proteins and help explain the efficacy of B cell-directed therapies in human disease.
引用
收藏
页码:4043 / 4051
页数:9
相关论文
共 55 条
[1]   Rituximab improves peripheral B cell abnormalities in human systemic lupus erythematosus [J].
Anolik, JH ;
Barnard, J ;
Cappione, A ;
Pugh-Bernard, AE ;
Felgar, RE ;
Looney, RJ ;
Sanz, I .
ARTHRITIS AND RHEUMATISM, 2004, 50 (11) :3580-3590
[2]   Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB) [J].
Bai, Donglin ;
del Corsso, Cristiane ;
Srinivas, Miduturu ;
Spray, David C. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 319 (03) :1452-1458
[3]   ISOLATION AND SELECTED PROPERTIES OF BLOOD MONOCYTES [J].
BENNETT, WE ;
COHN, ZA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1966, 123 (01) :145-&
[4]   Cell surface recycling of internalized antigen permits dendritic cell priming of B cells [J].
Bergtold, A ;
Desai, DD ;
Gavhane, A ;
Clyne, R .
IMMUNITY, 2005, 23 (05) :503-514
[5]   Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells [J].
Berwin, B ;
Hart, JP ;
Rice, S ;
Gass, C ;
Pizzo, SV ;
Post, SR ;
Nicchitta, CV .
EMBO JOURNAL, 2003, 22 (22) :6127-6136
[6]   Dendritic cells initiate immune control of Epstein-Barr virus transformation of B lymphocytes in vitro [J].
Bickham, K ;
Goodman, K ;
Paludan, C ;
Nikiforow, S ;
Tsang, ML ;
Steinman, RM ;
Münz, C .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (11) :1653-1663
[7]  
BOSWELL HS, 1980, J IMMUNOL, V124, P989
[8]   B cell depletion: a novel therapy for autoimmune diabetes? [J].
Bour-Jordan, Helene ;
Bluestone, Jeffrey A. .
JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (12) :3642-3645
[9]   Following immunization antigen becomes concentrated in a limited number of APCs including B cells [J].
Byersdorfer, CA ;
DiPaolo, RJ ;
Petzold, SJ ;
Unanue, ER .
JOURNAL OF IMMUNOLOGY, 2004, 173 (11) :6627-6634
[10]   B cells acquire particulate antigen in a macrophage-rich area at the boundary between the follicle and the subcapsular sinus of the lymph node [J].
Carrasco, Yolanda R. ;
Batista, Facundo D. .
IMMUNITY, 2007, 27 (01) :160-171