The role of B cells and antibodies in anti-tumour immunity is controversial. In some but not all human cancers, tumour-infiltrating B cells and the presence of tumour-specific antibodies correlate with prolonged survival, while both positive and negative effects have been reported in animal models. Here, we describe the multifaceted role of tumour-specific B cells in an in vivo model, and identify the contexts in which they act as either regulatory cells or anti-tumour effectors.
We have developed a mouse B16 melanoma model incorporating B cell receptor transgenic B cells. This enables us to track the development of tumour-specific B cells and antibodies with single cell resolution in vivo. Through the additional use of T cell receptor transgenic T cells, we are further able to assess the impact of T cell affinity and activation status on B cells responses and, conversely, to assess the effects of B cells on tumour-specific T cells.
We show that while tumour-specific IgM or IgG1 do not affect subcutaneous tumour growth or the number of lung metastases, lung metastases are decreased in the presence of a B cell response that generates high levels of tumour-specific IgG2a and IgG2b. Opposing this, we have shown that tumour-specific B cells may promote tumour growth via conversion of effector CD4 T cells to FoxP3+ regulatory T cells.
This is the first study to delineate the anti-tumour and immunosuppressive functions of B cells within a single model. Our results have implications for the development of immune checkpoint therapies that target tumour specific B cells.