Antigen-presenting human B cells are expanded in inflammatory conditions

被引:29
作者
Shimabukuro-Vornhagen, Alexander [1 ,2 ]
Garcia-Marquez, Maria [1 ,2 ]
Fischer, Rieke N. [1 ,2 ]
Iltgen-Breburda, Juliane [1 ,2 ]
Fiedler, Anne [1 ,2 ]
Wennhold, Kerstin [1 ,2 ]
Rappl, Gunter [3 ]
Abken, Hinrich [3 ]
Lehmann, Clara [2 ]
Herling, Marco [2 ]
Wolf, Dominik [4 ]
Faetkenheuer, Gerd [2 ]
Rubbert-Roth, Andrea [2 ]
Hallek, Michael [2 ]
Theurich, Sebastian [1 ,2 ]
von Bergwelt-Baildon, Michael [1 ,2 ]
机构
[1] Univ Hosp Cologne, Cologne Intervent Immunol, Kerpener Str 62, D-50937 Cologne, Germany
[2] Univ Hosp Cologne, Dept Internal Med, Cologne, Germany
[3] Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Cologne, Germany
[4] Univ Hosp Bonn, Dept Oncol Hematol & Rheumatol, Med Clin 3, Bonn, Germany
关键词
APC; rheumatoid arthritis; B cell subsets; inflammation; FC-GAMMA-RIIB; DENDRITIC CELLS; ACTIVATION; ARTHRITIS; CONTAIN; AUTOIMMUNITY; LYMPHOCYTES; REGULATORS; EXPRESSION; RECEPTORS;
D O I
10.1189/jlb.5A0416-182R
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Traditionally, B cells have been best known for their role as producers of antibodies. However, in recent years, a growing body of evidence has accumulated showing that B cells fulfill a range of other immunologic functions. One of the functions that has attracted increasing attention is the capacity of B cells to induce antigen-specific activation of T cells through presentation of antigens. However, the analysis of this B cell function has been hampered by the lack of a phenotypically well-defined antigen-presenting B cell subset. Here, we report the identification of a human antigen-presenting B cell subset with strong immunostimulatory properties. This B cell subset is characterized by low expression of CD21 and high expression of the activation marker CD86 and exhibits strong T cell-stimulatory activity, as demonstrated by means of an autologous mixed-lymphocyte reaction. Phenotypically, CD21(low)CD86(pos) immunostimulatory B cells (B-APC) represented CD27(+) class-switched IgM(neg)IgD(neg) B lymphocytes and displayed a higher expression of cell surface receptors, which mediate the migration from peripheral blood to sites of inflammation. Flow cytometric analysis of peripheral blood obtained from individuals with inflammatory conditions revealed that the B-APC subset was expanded following vaccination and in patients with rheumatoid arthritis. Taken together, our work shows that B-APC represents a strongly immunostimulatory B cell subset, which could be a promising target for immunotherapeutic intervention in inflammatory diseases.
引用
收藏
页码:577 / 587
页数:11
相关论文
共 53 条
[1]   Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab [J].
Alausa, M ;
Almagro, U ;
Siddiqi, N ;
Zuiderweg, R ;
Medipalli, R ;
Hariharan, S .
CLINICAL TRANSPLANTATION, 2005, 19 (01) :137-140
[2]   RETRACTED: Monoclonal IgG antibodies generated from joint-derived B cells of RA patients have a strong bias toward citrullinated autoantigen recognition (Retracted Article) [J].
Amara, Khaled ;
Steen, Johanna ;
Murray, Fiona ;
Morbach, Henner ;
Fernandez-Rodriguez, Blanca M. ;
Joshua, Vijay ;
Engstrom, Marianne ;
Snir, Omri ;
Israelsson, Lena ;
Catrina, Anca I. ;
Wardemann, Hedda ;
Corti, Davide ;
Meffre, Eric ;
Klareskog, Lars ;
Malmstrom, Vivianne .
JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (03) :445-455
[3]   EXPRESSION OF CD40 AND CD43 DURING ACTIVATION OF HUMAN LYMPHOCYTES-B [J].
BJORCK, P ;
AXELSSON, B ;
PAULIE, S .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1991, 33 (02) :211-218
[4]   CD19+CD24hiCD38hi B Cells Exhibit Regulatory Capacity in Healthy Individuals but Are Functionally Impaired in Systemic Lupus Erythematosus Patients [J].
Blair, Paul A. ;
Norena, Lina Yassin ;
Flores-Borja, Fabian ;
Rawlings, David J. ;
Isenberg, David A. ;
Ehrenstein, Michael R. ;
Mauri, Claudia .
IMMUNITY, 2010, 32 (01) :129-140
[5]   Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis [J].
Bolland, S ;
Ravetch, JV .
IMMUNITY, 2000, 13 (02) :277-285
[6]   Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset [J].
Charles, Edgar D. ;
Brunetti, Claudia ;
Marukian, Svetlana ;
Ritola, Kimberly D. ;
Talal, Andrew H. ;
Marks, Kristen ;
Jacobson, Ira M. ;
Rice, Charles M. ;
Dustin, Lynn B. .
BLOOD, 2011, 117 (20) :5425-5437
[7]   Fracture healing under healthy and inflammatory conditions [J].
Claes, Lutz ;
Recknagel, Stefan ;
Ignatius, Anita .
NATURE REVIEWS RHEUMATOLOGY, 2012, 8 (03) :133-143
[8]   B effector cells in rheumatoid arthritis and experimental arthritis [J].
Finnegan, Alison ;
Ashaye, Susan ;
Hamel, Keith M. .
AUTOIMMUNITY, 2012, 45 (05) :353-363
[9]   B Cell Receptor-Mediated Calcium Signaling Is Impaired in B Lymphocytes of Type Ia Patients with Common Variable Immunodeficiency [J].
Foerster, Christian ;
Voelxen, Nadine ;
Rakhmanov, Mirzokhid ;
Keller, Baerbel ;
Gutenberger, Sylvia ;
Goldacker, Sigune ;
Thiel, Jens ;
Feske, Stefan ;
Peter, Hans-Hartmut ;
Warnatz, Klaus .
JOURNAL OF IMMUNOLOGY, 2010, 184 (12) :7305-7313
[10]   A multhnerized form of recombinant human CD40 ligand supports long-term activation and proliferation of B cells [J].
Garcia-Marquez, Maria A. ;
Shimabukuro-Vornhagen, Alexander ;
Theurich, Sebastian ;
Kochanek, Matthias ;
Weber, Tanja ;
Wennhold, Kerstin ;
Dauben, Alexandra ;
Dzionek, Andrzej ;
Reinhard, Claudia ;
von Bergwelt-Baildon, Michael .
CYTOTHERAPY, 2014, 16 (11) :1537-1544