CD40 Ligand-activated, antigen-specific B cells are comparable to mature dendritic cells in presenting protein antigens and major histocompatibility complex class I- and class II-binding peptides.
Dendritic cells (DC) are increasingly exploited for cell-based immunotherapy. However, limitations in ex vivo DC growth and DC functional heterogeneity have motivated development of complementary antigen-presenting cell sources. Here, the ability of CD40 ligand (CD40L)-activated B cells to fulfil that role was investigated. We demonstrate for the first time that non-specific or antigen-specific murine B cells can be grown for extended periods of time by stimulation with CD40L. These cells rapidly up-regulate and maintain high levels of co-stimulatory molecules. In a head-to-head comparison with DC, CD40L-expanded B cells were comparable to DC in the presentation of peptides to CD4+ and CD8+ T cells. While DC were superior to antigen non-specific CD40L-activated B cells with regard to whole protein (NP-BSA) processing and presentation, CD40L-expanded B cells from NP-BSA-immunized mice were comparable to DC when presenting BSA or NP-BSA to primed primary T cells or when presenting NP linked to an unrelated carrier, CGG, to naïve T cells. Thus, the combination of CD40L activation, which supports B-cell growth and augments intracellular protein processing, and antigen uptake via the B-cell receptor, allows for efficient uptake, processing, and presentation of whole protein antigens in a fashion comparable to that observed with mature DC. Like DC, CD40L-activated B cells efficiently home to secondary lymphoid organs in vivo. This system represents a unique tool for studying primary antigen-specific B cells and the results suggest that the outgrowth of large numbers of highly activated B cells represents a viable and practical complement to DC for cell-based immunotherapy.
Ahmadi
Tahamtan
T
Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Flies
Amanda
A
Efebera
Yvonne
Y
Sherr
David H
DH
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine / Q000276:immunology; D005719:gamma-Globulins / Q000276:immunology
D018985:Epitopes, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D005719:gamma-Globulins; D023201:CD40 Ligand; D012710:Serum Albumin, Bovine