Submitted May 15, 2008
Accepted July 20, 2008
Targeting of antigens to B cells augments antigen-specific T cell responses and breaks immune tolerance to tumor-associated antigen MUC1
Chuanlin Ding, Li Wang, Jose Marroquin, and Jun Yan*
Tumor Immunobiology Program, University of Louisville, Louisville, KY, United States
* Corresponding author; email: jun.yan{at}louisville.edu.
B cells are antibody (Ab)-secreting cells as well as potent antigen (Ag)-presenting cells that prime T cell activation, which evokes great interest in their use for vaccine development. Here, we targeted ovalbumin (OVA) to B cells via CD19 and found that a single low dose of anti-CD19-OVA conjugates, but not isotype mAb-OVA, stimulated augmented CD4 and CD8 T cell proliferation and expansion. Administration of TLR9 agonist CpG could significantly enhance long-term T cell survival. Similar results were obtained when the tumor-associated Ag MUC1 was delivered to B cells. MUC1 transgenic (Tg) mice were previously found to lack effective T cell help and produce low-titer of anti-MUC1 Abs after vaccination. Targeting MUC1 to B cells elicited high-titer of anti-MUC1 Abs with different isotypes, predominantly IgG2a and IgG2b, in MUC1 Tg mice. The isotype switching of anti-MUC1 Ab was CD4-dependent. In addition, IFN-
-producing CD8 T cells and in vivo cytolytic activity were significantly increased in these mice. The mice also showed significant resistance to MUC1+ lymphoma cell challenge both in the prophylactic and therapeutic settings. We conclude that Ags targeting to B cells stimulate CD4 and CD8 T cell responses as well as Th-dependent humoral immune responses.
