Splenic B cells contribute to intraocular tumor progression

Abstract

Abstract Primary intraocular melanomas heavily infiltrated by CD8+ T cells and macrophages are generally larger, more heavily vascularized tumors with a genetic profile indicating greater risk of metastasis to the liver. To better understand how the tumoricidal activity of these immune cell populations is inhibited within the eye, a site of immune privilege, we developed a mouse model of intraocular tumor development in which immunogenic E.G7-OVA tumor cells transplanted in the anterior chamber form progressively growing intraocular tumors in C57Bl/6 mice despite infiltration by tumor-specific CD8+ T Cells and macrophages. Recently, we demonstrated that splenectomy prior to tumor challenge restored tumoricidal activity of CD8+ T cells and macrophages and promoted complete elimination of established intraocular tumors. Herein, we show that E.G7-OVA tumors transplanted in the eye of B cell deficient μMT mice are rejected by CD8+ T cells. The rejection of intraocular tumors in μMT mice was not due to abnormal splenic architecture but rather stemmed from the absence of tumor-specific B cells as mice transgenic for an immunoglobulin molecule to an irrelevant antigen (hen egg lysozyme) also rejected intraocular E.G7-OVA tumors. These data suggest that intraocular tumor development induces the generation of tumor-specific regulatory B cells (Breg) in the spleen. How these Breg contribute to intraocular tumor growth is not completely understood. However, intraocular E.G7-OVA tumors grew progressively in mice deficient in activation-induced cytidine deaminase that cannot undergo isotype class switching suggesting that secreted tumor specific IgG does not contribute to inhibiting tumoricidal activity within the eye.